Publications by authors named "Eui-Bae Jeung"

239 Publications

Prenatal Octamethylcyclotetrasiloxane Exposure Impaired Proliferation of Neuronal Progenitor, Leading to Motor, Cognition, Social and Behavioral Functions.

Int J Mol Sci 2021 Nov 30;22(23). Epub 2021 Nov 30.

Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Korea.

Cyclic siloxane octamethylcyclotetrasiloxane (D4) has raised concerns as an endocrine-disrupting chemical (EDC). D4 is widely used in detergent products, cosmetics, and personal care products. Recently, robust toxicological data for D4 has been reported, but the adverse effects of D4 on brain development are unknown. Here, pregnant mice on gestational day 9.5 were treated daily with D4 to postnatal day 28, and the offspring mice were studied. The prenatal D4-treated mice exhibited cognitive dysfunction, limited memory, and motor learning defect. Moreover, prenatal D4 exposure reduced the proliferation of neuronal progenitors in the offspring mouse brain. Next, the mechanisms through which D4 regulated the cell cycle were investigated. Aberrant gene expression, such as cyclin-dependent kinases CDK6 and cyclin-dependent kinase inhibitor p27, were found in the prenatal D4-treated mice. Furthermore, the estrogen receptors ERa and ERb were increased in the brain of prenatal D4-treated mice. Overall, these findings suggest that D4 exerts estrogen activity that affects the cell cycle progression of neuronal progenitor cells during neurodevelopment, which may be associated with cognitive deficits in offspring.
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http://dx.doi.org/10.3390/ijms222312949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8657511PMC
November 2021

Effect of quercetin on formation of porcine neutrophil extracellular trap.

Vet Immunol Immunopathol 2021 Nov 5;241:110335. Epub 2021 Oct 5.

Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea. Electronic address:

Neutrophil extracellular trap (NET) formation is an immune response to the invasion of external microorganisms. Quercetin, a member of the flavonoid family found in fruits and vegetables, has been examined in multiple biological contexts. The objective of this study was to examine the effect of quercetin on porcine NET formation. We measured NET formation by peripheral blood polymorphonuclear cells (PMNs) using propidium iodide (PI) dye. The amount of tumor necrosis factor (TNF)-α in culture supernatants was quantified by ELISA, and TNF-α mRNA expression was measured by RT-PCR. Direct treatment of PMNs with quercetin did not affect NET formation; however, NET formation was inhibited by exposure to culture supernatant from peripheral blood mononuclear cells (PBMCs) treated with quercetin. By contrast, culture supernatant from PBMCs treated with lipopolysaccharide (LPS) induced high levels of NET formation of PMNs, and this effect was reduced by co-treatment with LPS and quercetin. In addition, treatment of PMNs with recombinant porcine (rp) TNF-α induced high levels of NET formation. PBMCs treated with LPS increased higher levels of TNF-α mRNA and protein, but this effect was weakened when they were co-treated with quercetin. These findings indicated that quercetin inhibits NET formation of PMNs by suppressing production of TNF-α from LPS-stimulated PBMCs. These results suggest that quercetin exerts an anti-inflammatory effect, mediated by down-regulation of TNF-α production from LPS-stimulated PBMCs, which inhibits NET formation in PMNs.
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http://dx.doi.org/10.1016/j.vetimm.2021.110335DOI Listing
November 2021

Melatonin mitigates the adverse effect of hypoxia during myocardial differentiation in mouse embryonic stem cells.

J Vet Sci 2021 Jul;22(4):e54

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.

Background: Hypoxia causes oxidative stress and affects cardiovascular function and the programming of cardiovascular disease. Melatonin promotes antioxidant enzymes such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase.

Objectives: This study aims to investigate the correlation between melatonin and hypoxia induction in cardiomyocytes differentiation.

Methods: Mouse embryonic stem cells (mESCs) were induced to myocardial differentiation. To demonstrate the influence of melatonin under hypoxia, mESC was pretreated with melatonin and then cultured in hypoxic condition. The cardiac beating ratio of the mESC-derived cardiomyocytes, mRNA and protein expression levels were investigated.

Results: Under hypoxic condition, the mRNA expression of cardiac-lineage markers (, , and ) and melatonin receptor () was reduced. The mRNA expression of and the beating ratio of mESCs increased when melatonin was treated simultaneously with hypoxia, compared to when only exposed to hypoxia. Hypoxia-inducible factor (HIF)-1α protein decreased with melatonin treatment under hypoxia, and mRNA expression increased. When the cells were exposed to hypoxia with melatonin treatment, the protein expressions of phospho-extracellular signal-related kinase (p-ERK) and Bcl-2-associated X proteins (Bax) decreased, however, the levels of phospho-protein kinase B (p-Akt), phosphatidylinositol 3-kinase (PI3K), B-cell lymphoma 2 (Bcl-2) proteins, and antioxidant enzymes including Cu/Zn-SOD, Mn-SOD, and catalase were increased. Competitive melatonin receptor antagonist luzindole blocked the melatonin-induced effects.

Conclusions: This study demonstrates that hypoxia inhibits cardiomyocytes differentiation and melatonin partially mitigates the adverse effect of hypoxia in myocardial differentiation by regulating apoptosis and oxidative stress through the p-AKT and PI3K pathway.
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http://dx.doi.org/10.4142/jvs.2021.22.e54DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318788PMC
July 2021

Combined Exposure to Diazinon and Nicotine Exerts a Synergistic Adverse Effect In Vitro and Disrupts Brain Development and Behaviors In Vivo.

Int J Mol Sci 2021 Jul 20;22(14). Epub 2021 Jul 20.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.

A real-life environment during pregnancy involves multiple and simultaneous exposures to toxic chemicals. Perinatal exposures to toxic chemicals have been reported to exert an inhibitory effect on mouse neural development and behaviors. However, the effect of combined exposures of organophosphate and nicotine has not been previously reported. In this study, we investigated whether a combined exposure of diazinon and nicotine can have a synergistic effect. The effects of the combined chemical exposure on cell viability and neuronal differentiation were examined using mouse Sox1-GFP cells. Additionally, mice were maternally administered 0.18 mg/kg diazinon, a no adverse effect level (NOAEL) dose, combined with 0.4, 1, and 2 mg/kg nicotine. Mice offspring underwent behavior tests to assess locomotor, depressive, cognitive, and social behaviors. Morphological change in the brain was investigated with immunolocalization. We revealed that the combined exposure to diazinon and nicotine can have a synergistic adverse effect in vitro. In addition, the chemical-treated mouse offspring showed abnormalities in motor learning, compulsive-like behaviors, spatial learning, and social interaction patterns. Moreover, 0.18 mg/kg diazinon and 2 mg/kg nicotine co-exposure resulted in an increase in tyrosine hydroxylase (TH)-positive dopaminergic neurons. Thus, the findings suggest that perinatal co-exposure to nicotine and diazinon can result in abnormal neurodevelopment and behavior, even at low-level administration.
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http://dx.doi.org/10.3390/ijms22147742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307861PMC
July 2021

Establishment of a developmental neurotoxicity test by Sox1-GFP mouse embryonic stem cells.

Reprod Toxicol 2021 09 14;104:96-105. Epub 2021 Jul 14.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea. Electronic address:

Developmental toxicity tests have been generated by applying the embryonic stem cell tests at the European Centre for the Validation of Alternative Methods, or by using the embryoid body test in our laboratory. This study was undertaken to explore novel developmental neurotoxicity (DNT) assay, using a Sox1-GFP cell line (mouse embryonic stem cells with an endogenous Sox1-GFP reporter). The expression of Sox1, a marker for neuroepithelial cells, is detected by green fluorescence, and the fluorescence intensity is a critical factor for achieving neuronal differentiation. Sox1-GFP cells cultured for 24 h were exposed to eleven neurotoxicants and four non-neurotoxicants. CCK-8 assays were performed to determine IC values after 48 h of chemical treatment. The fluorescence intensity of GFP was measured 4 days after treating the cells, and it was observed to decrease after exposure to neurotoxicants at higher concentrations, thereby indicating that the neuronal differentiation of Sox1-GFP cells is inhibited by the chemicals. Taken together, the results obtained in this study provide a model for DNT using embryonic stem cells, which may be applied to evaluate the toxicity of new chemicals or new drug candidates.
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http://dx.doi.org/10.1016/j.reprotox.2021.07.004DOI Listing
September 2021

Loss of Nckx3 Exacerbates Experimental DSS-Induced Colitis in Mice through p53/NF-κB Pathway.

Int J Mol Sci 2021 Mar 5;22(5). Epub 2021 Mar 5.

Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Korea.

Inflammatory bowel diseases (IBDs) comprises a range of chronic inflammatory conditions of the intestinal tract. The incidence and prevalence of IBDs are increasing worldwide, but the precise etiology of these diseases is not completely understood. Calcium signaling plays a regulatory role in cellular proliferation. Nckx3, a potassium-dependent Na/Ca exchanger, is not only expressed in the brain but also in the aortic, uterine, and intestinal tissues, which contain abundant smooth muscle cells. This study investigated the role of Nckx3 in intestinal inflammation. Microarray analyses revealed the upregulation of the innate immune response-associated genes in the duodenum of Nckx3 knockout (KO) mice. The Nckx3 KO mice also showed an increase in IBD- and tumorigenesis-related genes. Using dextran sodium sulfate (DSS)-induced experimental colitis mice models, the Nckx3 KO mice showed severe colitis. Furthermore, the pathways involving p53 and NF-κB signaling were significantly upregulated by the absence of Nckx3. Overall, Nckx3 plays a critical role in the innate immune and immune response and may be central to the pathogenesis of IBD.
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http://dx.doi.org/10.3390/ijms22052645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961925PMC
March 2021

Comparison of steroid hormones in three different preeclamptic models.

Mol Med Rep 2021 04 4;23(4). Epub 2021 Feb 4.

Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Gyeongsangnam 50463, Republic of Korea.

Preeclampsia (PE) is a complication of pregnancy and is characterized by hypertension and proteinuria, threatening both the mother and the fetus. However, the etiology of PE has not yet been fully understood. Since the imbalance of steroid hormones is associated with the pathogenesis of PE, investigating steroidogenic mechanisms under various PE conditions is essential to understand the entire spectrum of pregnancy disorders. Therefore, the current study established three PE and models, and compared the levels of steroid hormones and steroidogenic enzymes within them. In cellular PE models induced by hypoxia, N‑nitro‑L‑arginine methyl ester hydrocholride (L‑NAME) and catechol‑o‑methyltransferase inhibitor, the levels of steroid hormones, including pregnenolone (P5), progesterone (P4), dehydroepiandrosterone (DHEA) and testosterone tended to decrease during steroidogenesis. Injection of L‑NAME in pregnant rats led to a reduction in the levels of estradiol and P4 through regulation of cholesterol side‑chain cleavage enzyme (CYP11A1) and 3β‑hydroxysteroid dehydrogenase/δ5 4‑isomerase type 1 (HSD3B1), whereas rats treated with COMT‑I exhibited elevated levels of P5 and DHEA by regulation of the CYP11A1 and aromatase cytochrome P450 (CYP19A1) in the placenta and plasma. The reduced uterine perfusion pressure operation decreased CYP11A1 and increased CYP19A1 expression in placental tissues, whereas steroid hormone levels were not altered. In conclusion, the results of the present study suggest that the induction of PE conditions dysregulates the steroid hormones via regulation of steroidogenic enzymes, depending on specific PE symptoms. These findings can contribute to the development of novel diagnostic and therapeutic modalities for PE, by monitoring and supplying appropriate levels of steroid hormones.
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http://dx.doi.org/10.3892/mmr.2021.11891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893799PMC
April 2021

4-tert-Octylphenol Exposure Disrupts Brain Development and Subsequent Motor, Cognition, Social, and Behavioral Functions.

Oxid Med Cell Longev 2020 17;2020:8875604. Epub 2020 Nov 17.

Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

The endocrine-disrupting chemical 4-tert-octylphenol (OP) is a widespread estrogenic chemical used in consumer products such as epoxy resins and polycarbonate plastic. However, the effects of OP on brain development are unknown. The present study examined the effects of OP on neuron and neurobehavioral development in mice. By using primary cortical neuron cultures, we found that OP-treated showed a decreased length of axons and dendrites and an increased number of primary and secondary dendrites. OP reduced bromodeoxyuridine (BrdU), mitotic marker Ki67, and phospho-histone H3 (p-Histone-H3), resulting in a reduction of neuronal progenitor proliferation in offspring mouse brain. Moreover, OP induced apoptosis in neuronal progenitor cells in offspring mouse brain. Furthermore, offspring mice from OP-treated dams showed abnormal cognitive, social, and anxiety-like behaviors. Taken together, these results suggest that perinatal exposure to OP disrupts brain development and behavior in mice.
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http://dx.doi.org/10.1155/2020/8875604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691001PMC
June 2021

Data on cytotoxicity of plant essential oils in A549 and Detroit 551 cells.

Data Brief 2020 Oct 16;32:106186. Epub 2020 Aug 16.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Chungbuk 28644, Republic of Korea.

To secure the safety for industrial applications of plant essential oils, it is necessary to determine the inhibitory concentration and inhibitory mechanism of cell proliferation in skin cells and lung cells. Considering inhalation through the respiratory system and skin contact of humans with essential oils, we used human lung cancer cells A549 and human skin fibroblasts Detroit 551 cells for all experiments. In this study, we examined IC values and protein levels of cell cycle markers (cyclin A, cyclin B, cyclin D, and cyclin E) and apoptosis marker (caspase-3) after exposure to 10 plant essential oils, including (L.) Des Moul, Thunb, var. (Maxim.) Kitam, (Fisch.&Mey.) Kuntze, L.f, Mill Thunb, L, (Siebold et Zucc.) Endl. var. Beissn. et Hochst, and Hort. ex Tanaka. After the treatment of A549 and Detroit 551 cells to varying concentrations of the 10 plant essential oils, IC values were determined by CCK analysis, whereas protein expressions of the four cyclins and caspase-3 were identified by Western blotting analysis. We believe that by examining the degree and mechanism of cell proliferation inhibition exerted by essential oils on skin and lung cells of humans, data obtained in this study can provide guidelines for the industrial application of plant essential oils.
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http://dx.doi.org/10.1016/j.dib.2020.106186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7452582PMC
October 2020

Perinatal Exposure to Triclosan Results in Abnormal Brain Development and Behavior in Mice.

Int J Mol Sci 2020 Jun 3;21(11). Epub 2020 Jun 3.

Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Korea.

Triclosan (TCS) is one of the most common endocrine-disrupting chemicals (EDCs) present in household and personal wash products. Recently, concerns have been raised about the association between abnormal behavior in children and exposure to EDC during gestation. We hypothesized that exposure to TCS during gestation could affect brain development. Cortical neurons of mice were exposed in vitro to TCS. In addition, we examined in vivo whether maternal TCS administration can affect neurobehavioral development in the offspring generation. We determined that TCS can impair dendrite and axon growth by reducing average length and numbers of axons and dendrites. Additionally, TCS inhibited the proliferation of and promoted apoptosis in neuronal progenitor cells. Detailed behavioral analyses showed impaired acquisition of spatial learning and reference memory in offspring derived from dams exposed to TCS. The TCS-treated groups also showed cognition dysfunction and impairments in sociability and social novelty preference. Furthermore, TCS-treated groups exhibited increased anxiety-like behavior, but there was no significant change in depression-like behaviors. In addition, TCS-treated groups exhibited deficits in nesting behavior. Taken together, our results indicate that perinatal exposure to TCS induces neurodevelopment disorder, resulting in abnormal social behaviors, cognitive impairment, and deficits in spatial learning and memory in offspring.
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http://dx.doi.org/10.3390/ijms21114009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7312693PMC
June 2020

Inhibitory effects of cigarette smoke extracts on neural differentiation of mouse embryonic stem cells.

Reprod Toxicol 2020 08 23;95:75-85. Epub 2020 May 23.

Laboratory of Biochemistry and Immunology, Republic of Korea. Electronic address:

Maternal smoking during the perinatal period is linked to adverse neonatal outcomes such as low birth weight and birth defects. Numerous studies have shown that cigarette smoke or nicotine exposure has a widespread effect on fetal nerve development. However, there exists a lack of understanding of what specific changes occur at the cellular level on persistent exposure to cigarette smoke during the differentiation of embryonic stem cells (ESCs) into neural cells. We previously investigated the effects of cigarette smoke extract (CSE) and its major component, nicotine, on the neural differentiation of mouse embryonic stem cells (mESCs). Differentiation of mESCs into neural progenitor cells (NPCs) or neural crest cells (NCCs) was induced with chemically defined media, and the cells were continuously exposed to CSE or nicotine during neural differentiation and development. Disturbed balance of the pluripotency state was observed in the NPCs, with consequent inhibition of neurite outgrowth and glial fibrillary acidic protein (Gfap) expression. These inhibitions correlated with the altered expression of proteins involved in the Notch-1 signaling pathways. The migration ability of NCCs was significantly decreased by CSE or nicotine exposure, which was associated with reduced protein expression of migration-related proteins. Taken together, we concluded that CSE and nicotine inhibit differentiation of mESCs into NPCs or NCCs, and may disrupt functional development of neural cells. These results imply that cigarette smoking during the perinatal period potentially inhibits neural differentiation and development of ESCs cells, leading to neonatal abnormal brain development and behavioral abnormalities.
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http://dx.doi.org/10.1016/j.reprotox.2020.05.010DOI Listing
August 2020

Calbindin-D is a Novel Risk Gene for Neurodegenerative Disease.

Cell Physiol Biochem 2020 May;54(3):438-456

Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea,

Background/aims: Calcium homeostasis plays a crucial role in neuronal development and disease. Calbindin-D (CaBP-9k) acts as calcium modulators and sensors in various tissues. However, the neurobiological functions of CaBP-9k are unknown.

Methods: We used CaBP-9k knockout (KO) mice to investigate the roles of these gene in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. We used anatomical and biochemical approaches to characterize functional abnormalities of the brain in the CaBP-9k KO mice.

Results: We found that the brains of CaBP-9k KO mice have increased APP/β-amyloid, Tau, and α-synuclein accumulation and endoplasmic reticulum (ER) stress-induced apoptosis. Neurons deficient for these CaBP-9k had abnormal intracellular calcium levels and responses. ER stress inhibitor TUDCA reduced ER stress-induced apoptosis and restored ER stress- and apoptosis-related proteins expression to wild-type levels in CaBP-9k KO mice. Furthermore, treatment with TUDCA rescued the abnormal memory and motor behaviors exhibited by older CaBP-9k KO mice.

Conclusion: Our results suggest that a loss of CaBP-9k may contribute to the onset and progression of neurodegenerative diseases.
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http://dx.doi.org/10.33594/000000229DOI Listing
May 2020

Cytostatic effects of plant essential oils on human skin and lung cells.

Exp Ther Med 2020 Mar 17;19(3):2008-2018. Epub 2020 Jan 17.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Essential oils are volatile compounds extracted from various plants by distillation, hydrodiffusion or compression. In recent years, the use of essential oils has gained popularity. Many pharmaceutical, cosmetic, sanitary, food industry and agriculture studies have revealed that essential oils exert antibacterial, antiviral, antifungal, antiparasitic, insecticidal, anticancer, neuroprotective, psychophysiological and anti-aging effects. Despite their reported uses, recent studies of eukaryotic cells have demonstrated that essential oils exert prooxidant and cytotoxic effects. Therefore, for the effective clinical use of essential oils, an evaluation of their cytotoxicity and the identification of the mechanisms affecting cell viability are required. To evaluate cytotoxicity, the present study determined the IC values of 15 essential oils provided by the Korea Forest Research Institute ( for. Uyeki, and ). Their effect was then assessed in human lung cells (A549) and human skin cells (Detroit 551) by performing cell counting kit-8 assays. To identify the mechanism associated with each oil's cytotoxicity, expressions of cytotoxicity-associated marker genes (cyclin A, cyclin B, cyclin D and cyclin E) involved in the cell cycle and caspase-3 (involved in cell death) were examined by performing reverse transcription-quantitative PCR and western blotting. In conclusion, plant essential oils can be used as a good source of medicine. However, without examining the safety of essential oils, they cannot be used in clinics. The results included estimates of the degree of cytotoxicity and the mechanism of cell death for each oil. It is expected that the data obtained from the current study will form guidelines for the clinically appropriate and safe use of these tested essential oils.
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http://dx.doi.org/10.3892/etm.2020.8460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027107PMC
March 2020

The effect of steroid hormone on the expression of the calcium-processing proteins in the immature female rat brain.

J Chem Neuroanat 2020 04 13;105:101767. Epub 2020 Feb 13.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea. Electronic address:

The cytosolic calcium concentration is regulated by calcium-processing proteins such as transient receptor potential cation channel subfamily V member 5 (TRPV5), TRPV6, sodium-calcium exchanger 1 (NCX1), and plasma membrane Ca ATPase 1 (PMCA1). Those calcium-processing proteins are important for physiological functions in the brain. The effects of steroid hormones on calcium-processing protein expressions in the brains are unknown. Thus, the effects of steroid hormones on the distribution, localization, and expressions of calcium-processing proteins in the brain were analyzed. Immature female rats were injected with estrogen (E2), progesterone (P4), dexamethasone (DEX), and their antagonists (ICI 182,780 and RU486). We found that TRPV5 and TRPV6 proteins were highly expressed in the cerebral cortex (CT), hypothalamus (HY), and brain stem (BS) compared to that in the olfactory bulb (OB) and cerebellum (CB). Also, the NCX1 protein was highly expressed in CT and BS compared to that in OB, HY, and CB, and PMCA1 protein was highly expressed in CT compared to that in other brain regions. Furthermore, expression levels of TRPV5, TRPV6, NCX1, and PMCA1 proteins were regulated by E2, P4, and/or DEX in the CT and HY. In summary, calcium-processing proteins are widely expressed in the immature rat brain, and expressions of calcium-processing proteins in CT and HY indicated that they may regulate by E2, P4, and/or DEX and can be attenuated by antagonist treatment. These results indicate that steroid hormone regulation of TRPV5, TRPV6, NCX1, and PMCA1 proteins may serve as a critical regulator of cytosolic calcium absorption and release in the brain.
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http://dx.doi.org/10.1016/j.jchemneu.2020.101767DOI Listing
April 2020

Dexamethasone Treatment Increases the Intracellular Calcium Level Through in A549 Cells.

Int J Mol Sci 2020 Feb 5;21(3). Epub 2020 Feb 5.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Korea.

This study investigated the effect of dexamethasone (DEX) on intracellular calcium levels and the expressions of transient receptor potential cation channel subcomponent V member 6 (), sodium-calcium exchanger 1 (), and plasma membrane calcium ATPase 1 () in A549 cells. The intracellular calcium level, by using the calcium indicator pGP-CMV-GCaMP6f, increased following DEX treatment for 6, 12, and 24 h in A549 cells. In addition, Rhod-4 assay after DEX treatment for 24 h showed that DEX increased the level of intracellular calcium. The expression of the calcium influx gene significantly increased, whereas the expressions of the calcium outflow and genes significantly decreased with DEX treatment. The mRNA levels of surfactant protein genes , , , and and the secreted airway mucin genes and were investigated by treating cells with DEX. The DEX treatment decreased the mRNA levels of and but increased the mRNA levels of and . The mRNA level was increased by DEX treatment, whereas mRNA was significantly decreased. These results indicate that DEX influences the intracellular calcium level through , and affects pulmonary surfactant genes and secreted airway mucin genes in A549 cells.
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http://dx.doi.org/10.3390/ijms21031050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7037905PMC
February 2020

The Protective Role of Calbindin-D on Endoplasmic Reticulum Stress-Induced Beta Cell Death.

Int J Mol Sci 2019 Oct 25;20(21). Epub 2019 Oct 25.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Korea.

Intracellular calcium ion content is tightly regulated for the maintenance of cellular functions and cell survival. Calbindin-D (CaBP-9k) is responsible for regulating the distribution of cytosolic free-calcium ions. In this study, we aimed to investigate the effect of CaBP-9k on cell survival in pancreatic beta cells. Six-month-old wildtype CaBP-9k, CaBP-28k, and CaBP-9k/28k knockout (KO) mice were used to compare the pathological phenotypes of calcium-binding protein-deleted mice. Subsequently, the endoplasmic reticulum (ER) stress reducer tauroursodeoxycholic acid (TUDCA) was administered to wildtype and CaBP-9k KO mice. In vitro assessment of the role of CaBP-9k was performed following CaBP-9k overexpression and treatment with the ER stress inducer thapsigargin. Six-month-old CaBP-9k KO mice showed reduced islet volume and up-regulation of cell death markers resulting from ER stress, which led to pancreatic beta cell death. TUDCA treatment recovered islet volume, serum insulin level, and abdominal fat storage by CaBP-9k ablation. CaBP-9k overexpression elevated insulin secretion and recovered thapsigargin-induced ER stress in the INS-1E cell line. The results of this study show that CaBP-9k can protect pancreatic beta cell survival from ER stress and contribute to glucose homeostasis, which can reduce the risk of type 1 diabetes and provide the molecular basis for calcium supplementation to diabetic patients.
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http://dx.doi.org/10.3390/ijms20215317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862009PMC
October 2019

Effects of cigarette smoke components on myocardial differentiation of mouse embryonic stem cells.

Environ Toxicol 2020 Jan 10;35(1):66-77. Epub 2019 Sep 10.

Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

The heart is the first organ formed in the developing fetus, and abnormal development of the heart is a major cause of fetal death. The adverse effects of cigarette smoke on the heart have been well established, but it is not well understood how cigarette smoke components regulate signaling molecules and cardiac specific functions during the early differentiation stage of the embryonic heart. In this study, we identified changes in the size of mouse embryoid bodies (mEBs) in response to treatment with cigarette smoke extract (CSE) via regulation of HDAC2, p53, p21, and cyclin D1 protein expression, which are cardiac differentiation and cell-cycle markers, respectively. In addition, exposure of mouse embryonic stem cells (mESCs) to cigarette smoke components inhibited myocardial differentiation and development through the expression of HDAC1, HDAC2, GATA4, NKX2-5, TBX5, HAND1, and Troponin I. Long-term exposure studies showed that CSE and nicotine may delay the development of mouse cardiomyocytes from mESCs and inhibit the contractibility, which is a fundamental function of the heart. Taken together, these findings suggest that cigarette smoke components, including nicotine, may affect abnormal myocardial differentiation and development.
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http://dx.doi.org/10.1002/tox.22843DOI Listing
January 2020

Sphingosine-1-phosphate (S1P) analog phytosphingosine-1-phosphate (P1P) improves the in vitro maturation efficiency of porcine oocytes via regulation of oxidative stress and apoptosis.

Mol Reprod Dev 2019 11 6;86(11):1705-1719. Epub 2019 Sep 6.

Sooam Biotech Research Foundation, Guro-gu, Seoul, Republic of Korea.

Phytosphingosine-1-phosphate (P1P) is a signaling sphingolipid that regulates various physiological activities. However, little is known about the effect of P1P in the context of reproduction. Thus, we aimed to investigate the influence of P1P on oocyte maturation during porcine in vitro maturation (IVM). Here, we report the expression of S1PR1-3 among P1P receptors (S1PR1-4) in cumulus cells and oocytes. When P1P was administered at concentrations of 10, 50, 100, and 1,000 nM during IVM, the metaphase II rate was significantly increased in the 1,000 nM (1 μM) P1P treatment group. Maturation rate improvement by P1P supplementation was observed only in the presence of epidermal growth factor (EGF). Oocytes under the influence of P1P showed decreased intracellular reactive oxygen species levels but no significant differences in glutathione levels. In our molecular studies, P1P treatment upregulated gene expression involved in cumulus expansion (Has2 and EGF), antioxidant enzymes (SOD3 and Cat), and developmental competence (Oct4) while activating extracellular signal-regulated kinase1/2 and Akt signaling. P1P treatment also influenced oocyte survival by shifting the ratio of Bcl-2 to Bax while inactivating JNK signaling. We further demonstrated that oocytes matured with P1P displayed significantly higher developmental competence (cleavage and blastocyst [BL] formation rate) and greater BL quality (total cell number and the ratio of apoptotic cells) when activated via parthenogenetic activation (PA) and in vitro fertilization. Despite the low levels of endogenous P1P found in animals, exogenous P1P influenced animal reproduction, as shown by increased porcine oocyte maturation as well as preimplantation embryo development. This study and its findings are potentially relevant for both human and animal-assisted reproduction.
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http://dx.doi.org/10.1002/mrd.23264DOI Listing
November 2019

Distribution of and steroid hormone effects on calbindin-D in the immature rat brain.

Brain Res Bull 2019 10 26;152:225-235. Epub 2019 Jul 26.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 362-763, Republic of Korea. Electronic address:

Calbindin-D (CaBP-9k), one of the major calcium-binding and calcium-buffering proteins, is important in the physiological functioning of organs. The neuroanatomical localization of CaBP-9k in the rodent brain has not been reported; thus, this study investigated the neuroanatomical distribution of CaBP-9k and the regulation of CaBP-9k expression on steroid hormones in the immature rat brain. To confirm the influence of steroid hormones on CaBP-9k expression, immature female rats were injected for 5 days with estrogen (E2), progesterone (P4), dexamethasone (DEX), and their antagonists (ICI 182, 780 and RU 486). The localization and expression of the CaBP-9k protein in brain regions were identified by immunofluorescence and western blot assays, respectively. We observed that CaBP-9k expression was especially strong in hypothalamus, cerebellum, and brain stem. In addition, CaBP-9k was colocalized with mature-, GABAergic, dopaminergic, and oxytocinergic neurons. We also observed that the CaBP-9k protein level was significantly increased by P4 and reversed by antagonist RU 486 treatment in immature rat brain. In summary, CaBP-9k positive cells have a wide distribution in the immature rat brain, and CaBP-9k expression is regulated by P4. We suggest that CaBP-9k expression regulated by steroid hormone may serve as an important regulator of cytosolic calcium concentration in the brain.
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http://dx.doi.org/10.1016/j.brainresbull.2019.07.028DOI Listing
October 2019

Effects of hydrocortisone administration on leptin and adiponectin synthesis in dogs.

Am J Vet Res 2019 Aug;80(8):771-778

Objective: To determine effects of hydrocortisone administration on serum leptin and adiponectin concentrations, abdominal fat distribution, and mRNA expression of leptin and adiponectin in abdominal adipose tissue of dogs.

Animals: 12 healthy dogs.

Procedures: Dogs received hydrocortisone (8.5 mg/kg; n = 6) or a placebo (6) orally every 12 hours for 90 days. Serum leptin and adiponectin concentrations were measured with a canine-specific ELISA on the day before (day 0; baseline) and during (days 1, 3, 7, 30, 60, and 90) administration. On days 0, 30, 60, and 90, abdominal fat mass was quantified with CT, and mRNA expression of leptin and adiponectin in abdominal fat was analyzed by use of a PCR assay.

Results: Hydrocortisone administration resulted in an increase in visceral fat mass on days 60 and 90, compared with the mass at baseline. Visceral fat mass at the level of L3 increased during hydrocortisone administration. Serum leptin concentration began to increase on day 1 and was significantly higher than the baseline concentration on days 30 and 60. Serum adiponectin concentration on days 30, 60, and 90 was significantly lower than the baseline concentration. Leptin and adiponectin mRNA expression in abdominal fat was greater on day 30, compared with expression at baseline, but lower on days 60 and 90, compared with expression on day 30. Serum leptin concentration and visceral fat mass were correlated.

Conclusions And Clinical Relevance: Hydrocortisone administration affected abdominal fat distribution and serum leptin and adiponectin concentrations through dysregulation of leptin and adiponectin expression.
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http://dx.doi.org/10.2460/ajvr.80.8.771DOI Listing
August 2019

Sex hormone-binding globulin suppresses NAFLD-triggered hepatocarcinogenesis after menopause.

Carcinogenesis 2019 08;40(8):1031-1041

College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.

It is generally accepted that androgen receptors increase the risk of hepatocellular carcinoma (HCC), and that estrogen reduces risk of HCC. Many studies regarding this have involved males. We, therefore, have focused our attention on females, especially postmenopausal females, who typically have limited supplies of estrogen. By using sex hormone-binding globulin (SHBG) transgenic mice, we produced a humanoid environment, and facilitated deposition and modulation of sex hormones. After exposure to diethylnitrosamine to induce HCC and upon reaching the age of 40 weeks, mice were fed the fat-rich diet for 5 months. Fat-rich diet fed or ovariectomized (OVX) wild-type mice aged 62 weeks showed HCC progression, whereas fat-rich diet fed SHBG mice or OVX SHBG mice displayed fewer tumors. In the liver of fat-rich diet fed SHBG mice, estrogenic conditions including high levels of 17β-estradiol and estrogen receptor alpha led to the induction of the lipogenesis inhibitor, phosphorylated acetyl-CoA carboxylase, and consequently suppressed fatty liver. The presence of plasma SHBG in HCC bearing mice suppressed the levels of steatosis and inflammation in a process mediated by estrogens and estrogen receptor alpha. Conversely, in the liver of OVX SHBG mice, lipogenic inhibition was also observed under conditions where the supply of estrogens is limited. Through in vitro experiment, it was confirmed SHBG suppresses lipogenesis via inhibition of acetyl-CoA carboxylase level. In conclusion, our results show that plasma SHBG might have a clinical impact on lipid-mediated hepatic diseases.
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http://dx.doi.org/10.1093/carcin/bgz107DOI Listing
August 2019

Rapamycin-induced autophagy decreases Myf5 and MyoD proteins in C2C12 myoblast cells.

Toxicol In Vitro 2019 Aug 21;58:132-141. Epub 2019 Mar 21.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea. Electronic address:

Rapamycin is an immunosuppressant that inhibits the mammalian or mechanistic target of rapamycin (mTOR) protein kinase and extends lifespan in organisms including mice. Myf5 and MyoD act as muscle-specific transcriptional factors for skeletal muscle differentiation. In this study, we determined whether rapamycin-induced autophagy causes the decrease of Myf5 and MyoD protein in C2C12 myoblast cells. Rapamycin induced a significant increase in the expression of the microtubule-associated protein 1 light chain 3 (LC3) II protein in a dose-dependent manner for 12 h. Rapamycin treatment also significantly increased p-ERK, p-Akt, and catalase expressions, and decreased Mn-SOD expression in a dose-dependent manner. Bax expression was significantly high compared to Bcl-2 expression in a dose-dependent manner of rapamycin for 12 h. For further study of rapamycin-induced autophagy in C2C12 myoblast cells, we investigated rapamycin treatment for 24, 36, and 48 h. Cell viability did not change with rapamycin treatment for 24, 36, and 48 h. Rapamycin-induced LC3-II, Beclin-1, Bax, and Bcl-2 proteins were significantly increased compared to without rapamycin. p-ERK expression increased with rapamycin treatment for 24 and 36 h compared to that without rapamycin, but decreased for 48 h. p-Akt expression decreased with rapamycin treatment for 36 and 48 h compared to that without rapamycin. In the same conditions, rapamycin-induced autophagy significantly reduced the Myf5 and MyoD proteins. Together, these results suggest that rapamycin-induced autophagy results in the decrease of Myf5 and MyoD proteins in C2C12 myoblast cells.
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http://dx.doi.org/10.1016/j.tiv.2019.03.025DOI Listing
August 2019

Apoptotic effects of cigarette smoke extracts on mouse embryonic stem cells via oxidative stress.

Environ Toxicol 2019 Jun 11;34(6):689-698. Epub 2019 Feb 11.

Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.

Previous studies have reported that cigarette smoke and cigarette smoke extract (CSE) have negative effects on embryonic development. However, no studies have investigated the mechanism through which CSE affects the cellular signaling pathway leading to apoptosis and oxidative stress in embryonic cells, or how the two pathways are cross-linked. Thus, we studied the effects of CSE on apoptosis and oxidative stress in mouse embryonic stem cells (mESCs). Specifically, we measured changes in cell viability in response to CSEs (3R4F and two domestic cigarettes CSE 1 and 2) using a water soluble tetrazolium (WST) assay and a neutral red uptake (NRU) assay, which revealed that cell viability decreased in a concentration-dependent manner. Western blot analysis revealed that the expression of cyclin D1 and cyclin E1 was decreased and that of p21 and p27 was increased by CSE. Additionally, the number of terminal deoxynucleotidyl transferase (TUNEL)-stained cells was increased by CSE, while the levels of Bax and Caspase-3 increased and Bcl-2 decreased. Moreover, a 2',7'-dichlorofluorescin diacetate (DCF-DA) assay and reactive oxygen species (ROS)-Glo H O assay confirmed that ROS were generated in response to CSE and that they were associated with up-regulated Keaf-1 and CHOP. Overall, the results revealed that cigarette smoke extract (CSE) inhibited cell proliferation by regulating cell cycle-related protein expression and increased oxidative stress by regulating the expression of Kelch-like ECH-associated protein 1 (Keap-1) and CCAAT/enhancer-binding protein homologous protein (CHOP), resulting in apoptosis in mESCs.
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http://dx.doi.org/10.1002/tox.22735DOI Listing
June 2019

Dietary intake of genistein suppresses hepatocellular carcinoma through AMPK-mediated apoptosis and anti-inflammation.

BMC Cancer 2019 Jan 3;19(1). Epub 2019 Jan 3.

College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Suite 401Veterinary medicine Bldg., Yuseong, Daejeon, 34134, South Korea.

Background: Women have a lower risk of hepatocellular carcinoma (HCC) than men, and the decreased possibility of HCC in women is thought to depend on estrogen levels. As a soybean-isoflavone product, genistein has estrogenic activity in various reproductive tissues, because it mimics 17β-estradiol and binds the estrogen receptor. Though genistein is a known liver cancer suppressor, its effects have not been studies in long-term experiment, where genistein is fed to a female animal model of HCC.

Methods: Mice were treated with diethylnitrosamine (DEN) to induce HCC at 2 weeks of age and fed with supplemental genistein for 5 months, from 40 to 62 weeks of age.

Results: The dietary intake of genistein decreased the incidence of HCC and suppressed HCC development. Genistein induced phospho-AMPK in total liver extracts, Hep3B cells, and Raw 264.7 cells, and phospho-AMPK promoted apoptosis in liver and Hep3B cells. Moreover, phospho-AMPK down-regulated pro-inflammatory responses and ameliorated liver damage. A suppressed pro-inflammatory response with increased mitochondrial respiration was concomitantly observed after genistein treatment.

Conclusions: Genistein-mediated AMPK activation increases hepatocyte apoptosis through energy-dependent caspase pathways, suppresses the inflammatory response in resident liver macrophages by increased cellular respiration, and consequently inhibits the initiation and progression of HCC.
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http://dx.doi.org/10.1186/s12885-018-5222-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6318960PMC
January 2019

Nitric oxide prevents HO-induced apoptosis in SK-N-MC human neuroblastoma cells.

Int J Biol Sci 2018 2;14(14):1974-1984. Epub 2018 Nov 2.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

Nitric oxide (NO) is a cellular signaling molecule in many physiological and pathological processes including neuroprotector. Here we examined the antiapoptotic effect of NO in SK-N-MC cells. HO treatment (10-200 μM) induced cell death in a dose-dependent manner and pretreatment of cells with 100 μM -nitroso--acetylpenicillamine (SNAP), an NO donor, attenuated the occurrence of HO-induced cell death. DAPI staining showed HO-induced nuclear fragmentation and NO treatment suppressed it. NO inhibited the proteolytic activation of caspase-3 and mitochondrial cytochrome c release. Treatment of soluble guanylyl cyclase inhibitor ODQ decreased the protective effect of SNAP on HO-treated cells and increased caspase 3-like enzyme activity and activation, cytochrome c release, PARP cleavage, and DNA fragmentation, indicating that cGMP is a key mediator in NO-mediated antiapoptosis. The cGMP analog 8-Br-cGMP blocked HO-induced apoptotic cell death; reduction of caspase-3 enzyme, cytochrome c release, and caspase-8 and -9. These preventive effects of SNAP and 8-Br-cGMP were suppressed by PKG inhibitor KT5823. Levels of PKGI, PKGII, and p-VASP proteins were increased by SNAP and 8-Br-cGMP and suppressed by KT5823 treatment. These results indicate that PKG is a downstream signal mediator in the suppression of apoptosis by NO and cGMP. Akt activation was inhibited the PI3K inhibitors LY294002 and Wortmannin, resulting in the inhibition of cell viability and increase of cytochrome c release. SNAP induced phosphorylation of Akt and Bad and then increased the interactions between 14-3-3β and p-Bad. These data suggest that the NO suppresses HO-induced SK-N-MC cell apoptosis by suppressing apoptosis signal mediating the interaction between 14-3-3β and Bad phosphorylation via PKG/PI3K/Akt.
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http://dx.doi.org/10.7150/ijbs.28050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299366PMC
September 2019

Role of inflammasome regulation on immune modulators.

J Biomed Res 2018 Nov;32(5):401-410

College of Veterinary Medicine and Institute of Veterinary Science.

Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery. Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin (IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor (TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain (NOD)-containing protein 2-like receptors (NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the inflammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.
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http://dx.doi.org/10.7555/JBR.32.20170120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6283823PMC
November 2018

Pregnenolone as a potential candidate for hormone therapy for female reproductive disorders targeting ERβ.

Mol Reprod Dev 2019 01 25;86(1):109-117. Epub 2018 Nov 25.

Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang, Gyeongsangnam, Republic of Korea.

Many steroid hormones such as estrogen (E2) bind to their receptors for the regulation of biological processes. Pregnenolone (P5) is the precursor form of almost all steroid hormones and is often used to treat skin disorders and neurological complications. However, the mechanism and physiological function of P5 in reproductive organs are not well established. In this study, we investigated the effects of P5 on activation and expression of E2 receptor (ER) in the uteri and ovaries. To study the mechanism of P5 directly, Ishikawa cells were transfected with E2 response element (ERE)-luciferase plasmid and isoforms of ER. ERE-luciferase activity induced by P5 was similar to that induced by E2, and P5 showed high activity for ERβ without any relevance to P5-metabolizing hormones such as progesterone (P4) and E2. In an animal study, immature female rats treated with P5 showed upregulation of ERα and downregulation of ERβ in the uteri, which is the main organ expressing ERα. In ERβ-expressing organ ovaries, estrogen receptor 1, estrogen receptor 2, and P4 receptor were all downregulated by P5 and E2. Also, a decrease of ovarian cell proliferation and viability was observed in response to P5 relative to the control, suggesting that P5 may be a candidate for antiproliferative hormone of ovarian cancer. These findings suggest that P5 stimulates ERE promoter by ERβ-mediated signaling in the uteri and ovaries. Activation of ERβ by P5 may help in understanding the mechanism of ER-related female reproductive diseases such as endometriosis and ovarian cancer.
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http://dx.doi.org/10.1002/mrd.23086DOI Listing
January 2019

Alleviation effects of natural volatile organic compounds from and on systemic and pulmonary inflammation.

Biomed Rep 2018 Nov 12;9(5):405-414. Epub 2018 Sep 12.

Laboratory of Veterinary Biochemistry and Molecular Biology, Veterinary Medical Center and College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.

() and () have been traditionally used as antibiotic, antinociceptive and anti-inflammatory agents in Asian folk medicine. Recent studies have demonstrated antioxidant, antiproliferative and anti-inflammatory effects of and extracts. In the present study, volatile organic compounds (VOCs) of and were examined to determine whether they have anti-inflammatory capabilities. To evaluate the anti-inflammatory effects of VOCs of and , lipopolysaccharide (LPS) was administered to the lung by nasal injection and to the whole body by intraperitoneal injection. Alterations in serum immunoglobulin E (IgE) levels and prostaglandin E2 (PgE2) were examined using ELISA. LPS-increased serum IgE and PgE2 levels were recovered by administration of dexamethasone and VOCs of and . Levels of mRNA expression of inflammatory cytokines were determined in an LPS-induced inflammation mouse model. Reverse transcription-quantitative polymerase chain reaction was used to determine the mRNA expression levels of cyclooxygenase 2, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and IL-13 in peripheral blood mononuclear cells. The expression of all examined cytokine mRNAs increased by LPS was suppressed by dexamethasone and VOCs of and . Similar tendencies were observed in lung tissues and cells obtained via bronchoalveolar lavage. The results of the present study suggested that VOCs of and , through their immunosuppressive activities, may have therapeutic potential in the treatment or prevention of inflammation.
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http://dx.doi.org/10.3892/br.2018.1147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6200960PMC
November 2018

Pre-validation study of alternative developmental toxicity test using mouse embryonic stem cell-derived embryoid bodies.

Food Chem Toxicol 2019 Jan 16;123:50-56. Epub 2018 Oct 16.

Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea. Electronic address:

The embryoid body test (EBT) is a developmental toxicity test method that assesses the half inhibitory concentrations of substances in the area of embryoid bodies (EBs), and in the viability of mouse embryonic stem cells (ESCs) and fibroblasts (3T3 cells) following chemical exposure for three and four days, respectively. In the previous study, the EBT showed more advanced than the embryonic stem cell test (EST) from the European Centre for the Validation of Alternative Methods (ECVAM) applying cardiac differentiation of mouse ESCs, because the EBT greatly reduced the exposure time, labor, and amount of materials required, and misclassification of embryotoxic potential. This pre-validation study evaluated the predictive accuracy of the EBT using 26 coded test substances by two steps: intra-laboratory and inter-laboratory reproducibility tests. Since some substances have different embryotoxic potentials at different pregnancy periods, in this study, a new prediction model consisting of non-toxic and toxic classes was used, instead of the existing prediction model assessing embryotoxicants in four classes. The results of the intra- and inter-laboratory tests were highly accurate (above 80%) when substances were classified using the predictive model. In conclusion, EBT can accurately classify various embryotoxicants in a short time with less effort and greater validation.
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http://dx.doi.org/10.1016/j.fct.2018.10.044DOI Listing
January 2019
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