Publications by authors named "Hossam H Shawki"

15 Publications

  • Page 1 of 1

Attitudes Toward Psychological Disorders and Alternative Medicine in Saudi Participants.

Front Psychiatry 2021 12;12:577103. Epub 2021 Feb 12.

Department of Biological Sciences, Faculty of Science, King Abdulaziz University (KAU), Jeddah, Saudi Arabia.

This study was designed to investigate Saudis' attitudes toward mental distress and psychotropic medication, attribution of causes, expected side effects, and to analyze participants' expectations toward alternative or complementary medicine using aromatic and medicinal plants, through a survey. The study included 674 participants (citizens and residents in Saudi Arabia) who were randomly contacted via email and social media and gave their consent to complete a questionnaire dealing with 39 items that can be clustered in six parts. Descriptive statistics and Chi-square for cross-tabulation were generated using SPSS. Among the 664 participants, 73.4% believed that there are some positive and negative outcomes of psychotropic medication. Participants (72.0%) think that the most important reason leading to psychological disorders is mainly due to the loss of a relative or beloved person, and 73.9% considered psychic session as one of the possible treatments of psychological disorders. Surprisingly, only 18.8% of the participants agreed that medicinal and aromatic plants could be a possible treatment of the psychological disorder. Participants (82%) consider that physicians are the most trustful and preferred source of information about alternative and complementary medicine.
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http://dx.doi.org/10.3389/fpsyt.2021.577103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907434PMC
February 2021

Polydatin mitigates pancreatic β-cell damage through its antioxidant activity.

Biomed Pharmacother 2021 Jan 26;133:111027. Epub 2020 Nov 26.

Department of Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Japan. Electronic address:

Several reports have been shown the pivotal role of oxidative stress in the progression of diabetes mellitus and its complications. Polydatin (PD), a natural phytochemical, has wide range of pharmacological actions, however, the underlying beneficial effects in pancreas was not clarified. In the current study, using in vivo and in vitro models, we investigated the possible protective effects of PD against oxidative damage in pancreatic β-cells. Diabetic rats were examined after oral administration with PD (50 mg/kg b.wt.) for 28 days. Results revealed that PD significantly enhanced glucose tolerance and insulin secretion in the bloodstream of diabetic rats as well as lipid metabolism. Interestingly, in vivo results indicated that PD decreased the lipid peroxidation, improved the antioxidant status, and inhibited the inflammation in pancreas. Alongside, we artificially induced oxidative stress by exposing the insulin-producing RINm5F cells to hydrogen peroxide in the presence or absence of PD. The co-treatment with PD preserved cell viability, reduced ROS accumulation, as well as enhanced the anti-oxidant, anti-apoptotic, and cell function markers. To conclude, PD exhibited potential action in preserving β-cell function and inhibiting oxidative damage probably through its antioxidant properties. Thus, PD could be a possible therapeutic agent for diabetic patients.
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http://dx.doi.org/10.1016/j.biopha.2020.111027DOI Listing
January 2021

Transcription factor MafB in podocytes protects against the development of focal segmental glomerulosclerosis.

Kidney Int 2020 08 28;98(2):391-403. Epub 2020 Apr 28.

Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan; Laboratory Animal Resource Center (LARC), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Ibaraki, Japan; Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Ibaraki, Japan. Electronic address:

Focal segmental glomerulosclerosis (FSGS) is a common cause of steroid-resistant nephrotic syndrome. Spontaneous remission of FSGS is rare and steroid-resistant FSGS frequently progresses to renal failure. Many inheritable forms of FSGS have been described, caused by mutations in proteins that are important for podocyte function. Here, we show that a basic leucine zipper transcription factor, MafB, protects against FSGS. MAFB expression was found to be decreased in the podocytes of patients with FSGS. Moreover, conditional podocyte-specific MafB-knockout mice developed FSGS with massive proteinuria accompanied by depletion of the slit diaphragm-related proteins (Nphs1 and Magi2), and the podocyte-specific transcription factor Tcf21. These findings indicate that MafB plays a crucial role in the pathogenesis of FSGS. Consistent with this, adriamycin-induced FSGS and attendant proteinuria were ameliorated by MafB overexpression in the podocytes of MafB podocyte-specific transgenic mice. Thus, MafB could be a new therapeutic target for FSGS.
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http://dx.doi.org/10.1016/j.kint.2020.02.038DOI Listing
August 2020

CRISPR/Cas9-based genome editing in mice uncovers 13 testis- or epididymis-enriched genes individually dispensable for male reproduction†.

Biol Reprod 2020 08;103(2):183-194

Department of Experimental Genome Research, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan.

Developing a safe and effective male contraceptive remains a challenge in the field of medical science. Molecules that selectively target the male reproductive tract and whose targets are indispensable for male reproductive function serve among the best candidates for a novel non-hormonal male contraceptive method. To determine the function of these genes in vivo, mutant mice carrying disrupted testis- or epididymis-enriched genes were generated by zygote microinjection or electroporation of the CRISPR/Cas9 components. Male fecundity was determined by consecutively pairing knockout males with wild-type females and comparing the fecundity of wild-type controls. Phenotypic analyses of testis appearance and weight, testis and epididymis histology, and sperm movement were further carried out to examine any potential spermatogenic or sperm maturation defect in mutant males. In this study, we uncovered 13 testis- or epididymis-enriched evolutionarily conserved genes that are individually dispensable for male fertility in mice. Owing to their dispensable nature, it is not feasible to use these targets for the development of a male contraceptive.
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http://dx.doi.org/10.1093/biolre/ioaa083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401351PMC
August 2020

Pomegranate Seeds Extract Possesses a Protective Effect against Tramadol-Induced Testicular Toxicity in Experimental Rats.

Biomed Res Int 2020 9;2020:2732958. Epub 2020 Mar 9.

Department of Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Tramadol is a centrally acting opioid analgesic that is extensively used. The chronic exposure to tramadol induces oxidative stress and toxicity especially for patients consuming it several times a day. Previously, we and others reported that tramadol induces testicular damage in rats. This study was conducted to investigate the possible protective effect of pomegranate seed extract (PgSE) against tramadol-induced testicular damage in adult and adolescent rats. Male rats were orally treated with tramadol or in a combination with PgSE for three weeks. Testes were then dissected and analyzed. Histological and ultrastructural examinations indicated that tramadol induced many structural changes in the testes of adult and adolescent rats including hemorrhage of blood vessels, intercellular spaces, interstitial vacuoles, exfoliation of germ cells in lumen, cell apoptosis, chromatin degeneration of elongated spermatids, and malformation of sperm axonemes. Interestingly, these abnormalities were not observed in tramadol/PgSE cotreated rats. The morphometric analysis revealed that tramadol disrupted collagen metabolism by elevating testicular levels of collagen fibers but that was protected in tramadol/PgSE cotreatment at both ages. In addition, DNA ploidy revealed that S phase of the cell cycle was diminished when adult and adolescent rats were treated with tramadol. However, the S phase had a normal cell population in the cotreated adult rats, but adolescent rats had a lower population than controls. Furthermore, the phytochemistry of PgSE revealed a high content of total polyphenols and total flavonoids within this extract; besides, the DPPH free radical scavenging activity was high. In conclusion, this study indicated that PgSE has a prophylactic effect against tramadol-induced testicular damage in both adult and adolescent ages, although the tramadol toxicity was higher in adolescent age to be completely protected. This prophylactic effect might be due to the high antioxidant compounds within the pomegranate seeds.
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http://dx.doi.org/10.1155/2020/2732958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085358PMC
December 2020

MafB Is Important for Pancreatic β-Cell Maintenance under a MafA-Deficient Condition.

Mol Cell Biol 2019 09 12;39(17). Epub 2019 Aug 12.

Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan

The pancreatic-islet-enriched transcription factors MafA and MafB have unique expression patterns in β cells in rodents. MafA is specifically expressed in β cells and is a key regulatory factor for maintaining adult β-cell function, whereas MafB plays an essential role in β-cell development during embryogenesis, and its expression in β cells gradually decreases and is restricted to α cells after birth in rodents. However, it was previously observed that MafB started to be reexpressed in insulin-positive (insulin) β cells in MafA-deficient adult mice. To elucidate how MafB functions in the adult β cell under MafA-deficient conditions, we generated MafA and MafB double-knockout (A0B0) mice in which MafB was specifically deleted from β cells. As a result, the A0B0 mice became more vulnerable to diabetes under a high-fat diet (HFD) treatment, with impaired islet formation and a decreased number of insulin β cells because of increased β-cell apoptosis, indicating MafB can take part in the maintenance of adult β cells under certain pathological conditions.
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http://dx.doi.org/10.1128/MCB.00080-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692125PMC
September 2019

EFCAB2 is a novel calcium-binding protein in mouse testis and sperm.

PLoS One 2019 1;14(4):e0214687. Epub 2019 Apr 1.

Department of Comparative and Experimental Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Calcium-binding proteins regulate ion metabolism and the necessary signaling pathways for the maturational events of sperm. Our aim is to identify the novel calcium-binding proteins in testis. The gene EFCAB2 (GenBank NM_026626.3, NP_080902.1) was not previously examined, and its properties and exact mechanisms of action are unknown. In this study, we performed phylogenetic and structure prediction analyses of EFCAB2, which displays definitive structural features. Additionally, the distribution, localization, and calcium binding ability of mouse EFCAB2 were investigated. Results revealed extensive conservation of EFCAB2 among different eukaryotic orthologs. The constructed 3D model predicted that mouse EFCAB2 contains seven α-helices and two EF-hand motifs. The first EF-hand motif is located in N-terminal, while the second is located in C-terminal. By aligning the 3D structure of Ca2+-binding loops from EFCAB2 with calmodulin, we predicted six residues that might be involved in Ca2+ binding. The distribution of the Efcab2 mRNA, as determined by northern blotting, was detected only in the testis among mouse tissues. Native and recombinant EFCAB2 protein were detected by western blotting as one band at 20 kDa. In situ hybridization and immunohistochemical analyses showed its localization specifically in spermatogenic cells from primary spermatocytes to elongate spermatids within the seminiferous epithelium, but neither spermatogonia nor somatic cells were expressed. Moreover, EFCAB2 was specifically localized to the principal piece of cauda epididymal sperm flagellum. Furthermore, the analyses of purified recombinant EFCAB2 by Stains-all, ruthenium red staining, and by applying in vitro autoradiography assay showed that the physiological function of this protein is Ca2+ binding. These results suggested that EFCAB2 might be involved in the control of sperm flagellar movement. Altogether, here we describe about EFCAB2 as a novel calcium-binding protein in mouse testis and sperm.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214687PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443151PMC
January 2020

Leaves Extracts Induce Apoptosis and Cell Cycle Arrest of Hepatocellular Carcinoma.

Biomed Res Int 2019 1;2019:2698570. Epub 2019 Jan 1.

Department of Chemistry, Faculty of Science, Cairo University, 12613 Giza, Egypt.

Moringa grows in the tropical and subtropical regions of the world. The genus belongs to family Moringaceae. It is found to possess various medicinal uses including hypoglycemic, analgesic, anti-inflammatory, hypolipidemic, and antioxidant activities. In this study, we investigated the antimicrobial and the anticancer activity of the as well as leaves extracts grown locally in Egypt. Results indicated that most of the extracts were found to possess high antimicrobial activity against gram-positive bacteria, gram-negative bacteria, and fungus. The survival rate of cancer cells was decreased in both hepatocellular carcinoma (HepG2) and breast carcinoma (MCF-7) cell lines when treated with leaves extracts. In addition, the cell cycle progression, apoptosis, and cancer-related genes confirmed its anticancer effect. The toxicity of each extract was also tested using the normal melanocytes cell line HFB4. The toxicity was low in both and leaves extracts. Furthermore, GC/MS analysis fractionized the phytochemicals content for each potential extract. In conclusion, results suggested that the and leaves extracts possess antimicrobial and anticancer properties which could be attributed to the bioactive phytochemical compounds present inside the extracts from this plant. These findings can be used to develop new drugs, especially for liver cancer chemotherapy.
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http://dx.doi.org/10.1155/2019/2698570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6332967PMC
May 2019

Aberrant imprinting in mouse trophoblast stem cells established from somatic cell nuclear transfer-derived embryos.

Epigenetics 2018 23;13(7):693-703. Epub 2018 Aug 23.

a RIKEN BioResource Research Center , Tsukuba , Ibaraki , Japan.

Although phenotypic abnormalities frequently appear in the placenta following somatic cell nuclear transfer (SCNT), mouse trophoblast stem cells (TSCs) established from SCNT embryos reportedly show no distinct abnormalities compared with those derived from normal fertilization. In this study, we reexamined SCNT-TSCs to identify their imprinting statuses. Placenta-specific maternally imprinted genes (Gab1, Slc38a4, and Sfmbt2) consistently showed biallelic expression in SCNT-TSCs, suggesting their loss of imprinting (LOI). The LOI of Gab1 was associated with decreased DNA methylation, and that of Sfmbt2 was associated with decreased DNA methylation and histone H3K27 trimethylation. The maternal allele of the intergenic differentially methylated region (IG-DMR) was aberrantly hypermethylated following SCNT, even though this region was prone to demethylation in TSCs when established in a serum-free chemically defined medium. These findings indicate that the development of cloned embryos is associated with imprinting abnormalities specifically in the trophoblast lineage from its initial stage, which may affect subsequent placental development.
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http://dx.doi.org/10.1080/15592294.2018.1507199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224209PMC
March 2019

MAFB is dispensable for the fetal testis morphogenesis and the maintenance of spermatogenesis in adult mice.

PLoS One 2018 11;13(1):e0190800. Epub 2018 Jan 11.

Department of Anatomy and Embryology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan.

The transcription factor MAFB is an important regulator of the development and differentiation of various organs and tissues. Previous studies have shown that MAFB is expressed in embryonic and adult mouse testes and is expected to act as the downstream target of retinoic acid (RA) to initiate spermatogenesis. However, its exact localization and function remain unclear. Here, we localized MAFB expression in embryonic and adult testes and analyzed its gene function using Mafb-deficient mice. We found that MAFB and c-MAF are the only large MAF transcription factors expressed in testes, while MAFA and NRL are not. MAFB was localized in Leydig and Sertoli cells at embryonic day (E) 18.5 but in Leydig cells, Sertoli cells, and pachytene spermatocytes in adults. Mafb-deficient testes at E18.5 showed fully formed seminiferous tubules with no abnormal structure or differences in testicular somatic cell numbers compared with those of control wild-type mice. Additionally, the expression levels of genes related to development and function of testicular cells were unchanged between genotypes. In adults, the expression of MAFB in Sertoli cells was shown to be stage specific and induced by RA. By generating Mafbfl/fl CAG-CreER™ (Mafb-cKO) mice, in which Cre recombinase was activated upon tamoxifen treatment, we found that the neonatal cKO mice died shortly upon Mafb deletion, but adult cKO mice were alive upon deletion. Adult cKO mice were fertile, and spermatogenesis maintenance was normal, as indicated by histological analysis, hormone levels, and germ cell stage-specific markers. Moreover, there were no differences in the proportion of seminiferous stages between cKO mice and controls. However, RNA-Seq analysis of cKO Sertoli cells revealed that the down-regulated genes were related to immune function and phagocytosis activity but not spermatogenesis. In conclusion, we found that MAFB is dispensable for fetal testis morphogenesis and spermatogenesis maintenance in adult mice, despite the significant gene expression in different cell types, but MAFB might be critical for phagocytosis activity of Sertoli cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190800PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5764304PMC
February 2018

Transcription factor MafB may play an important role in secondary hyperparathyroidism.

Kidney Int 2018 01 28;93(1):54-68. Epub 2017 Sep 28.

Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan; Laboratory Animal Resource Center (LARC), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan; International Institute for Integrative Sleep Medicine (WPI-IIIS), Faculty of Medicine, University of Tsukuba, Ibaraki, Japan; Life Science Center of Tsukuba Advanced Research Alliance (TARA), Faculty of Medicine University of Tsukuba, Ibaraki, Japan.

The transcription factor MafB is essential for development of the parathyroid glands, the expression of which persists after morphogenesis and in adult parathyroid glands. However, the function of MafB in adult parathyroid tissue is unclear. To investigate this, we induced chronic kidney disease (CKD) in wild-type and MafB heterozygote (MafB+/-) mice by feeding them an adenine-supplemented diet, leading to secondary hyperparathyroidism. The elevated serum creatinine and blood urea nitrogen levels in heterozygous and wild-type mice fed the adenine-supplemented diet were similar. Interestingly, secondary hyperparathyroidism, characterized by serum parathyroid hormone elevation and enlargement of parathyroid glands, was suppressed in MafB+/- mice fed the adenine-supplemented diet compared to similarly fed wild-type littermates. Quantitative RT-PCR and immunohistochemical analyses showed that the increased expression of parathyroid hormone and cyclin D2 in mice with CKD was suppressed in the parathyroid glands of heterozygous CKD mice. A reporter assay indicated that MafB directly regulated parathyroid hormone and cyclin D2 expression. To exclude an effect of a developmental anomaly in MafB+/- mice, we analyzed MafB tamoxifen-induced global knockout mice. Hypocalcemia-stimulated parathyroid hormone secretion was significantly impaired in MafB knockout mice. RNA-sequencing analysis indicated PTH, Gata3 and Gcm2 depletion in the parathyroid glands of MafB knockout mice. Thus, MafB appears to play an important role in secondary hyperparathyroidism by regulation of parathyroid hormone and cyclin D2 expression. Hence, MafB may represent a new therapeutic target in secondary hyperparathyroidism.
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http://dx.doi.org/10.1016/j.kint.2017.06.023DOI Listing
January 2018

CABCOCO1, a novel coiled-coil protein With calcium-binding activity, is localized in the sperm flagellum.

Mol Reprod Dev 2016 10 28;83(10):912-926. Epub 2016 Mar 28.

Laboratory of Reproductive Biochemistry, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.

The gene 1700040L02Rik (GenBank accession number NM_028491, NP_082767.1) was selected by in silico screening as candidate that encodes a calcium-binding protein in sperm from a database of predicted mouse cilia-related genes. The predicted amino acid sequence revealed the presence of coiled-coil domain at the C-terminus and a CLAMP motif containing a leucine zipper domain in the middle of the protein. Assessment of a recombinant version of this protein by Stains-all and ruthenium red staining and by direct measurement of terbium binding revealed its calcium-binding activities. We therefore named this protein CABCOCO1 for calcium-binding coiled-coil protein-1. Immunohistochemical analyses showed its localization in spermatogenic cells of mouse testis. CABCOCO1 was first observed in the cytoplasm of murine spermatocytes, concentrated around centrioles of spermatids and co-localized with the centrosomal protein pericentrin. During the stage when centrosome number is reduced, CABCOCO1 relocalized to the murine sperm flagellum. On the other hand, in porcine sperm, whose proximal centriole remains intact while the distal centriole degenerates during spermiogenesis, CABCOCO1 localized both in the basal body and the flagellum. These results suggested that CABCOCO1 is involved in the control of sperm flagellar movement. Mol. Reprod. Dev. 83: 912-926, 2016 © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/mrd.22639DOI Listing
October 2016

Germline recombination in a novel Cre transgenic line, Prl3b1-Cre mouse.

Genesis 2016 07 13;54(7):389-97. Epub 2016 May 13.

Laboratory Animal Resource Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Spermatogenesis is a complex and highly regulated process by which spermatogonial stem cells differentiate into spermatozoa. To better understand the molecular mechanisms of the process, the Cre/loxP system has been widely utilized for conditional gene knockout in mice. In this study, we generated a transgenic mouse line that expresses Cre recombinase under the control of the 2.5 kbp of the Prolactin family 3, subfamily b, member 1 (Prl3b1) gene promoter (Prl3b1-cre). Prl3b1 was initially reported to code for placental lactogen 2 (PL-2) protein in placenta along with increased expression toward the end of pregnancy. PL-2 was found to be expressed in germ cells in the testis, especially in spermatocytes. To analyze the specificity and efficiency of Cre recombinase activity in Prl3b1-cre mice, the mice were mated with reporter R26GRR mice, which express GFP ubiquitously before and tdsRed exclusively after Cre recombination. The systemic examination of Prl3b1-cre;R26GRR mice revealed that tdsRed-positive cells were detected only in the testis and epididymis. Fluorescence imaging of Prl3b1-cre;R26GRR testes suggested that Cre-mediated recombination took place in the germ cells with approximately 74% efficiency determined by in vitro fertilization. In conclusion, our results suggest that the Prl3b1-cre mice line provides a unique resource to understand testicular germ-cell development. genesis 54:389-397, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/dvg.22944DOI Listing
July 2016

Identification, localization, and functional analysis of the homologues of mouse CABS1 protein in porcine testis.

Exp Anim 2016 Jul 8;65(3):253-65. Epub 2016 Mar 8.

Laboratory of Reproductive Biochemistry, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

Previously, we have identified a calcium-binding protein that is specifically expressed in spermatids and localized to the flagella of the mature sperm in mouse, so-called mCABS1. However, the physiological roles of CABS1 in the male reproductive system have not been fully elucidated yet. In the current study, we aimed to localize and clarify the role of CABS1 in porcine (pCABS1). We determined for the first time the full nucleotides sequence of pCABS1 mRNA. pCABS1 protein was detected on SDS-PAGE gel as two bands at 75 kDa and 70 kDa in adult porcine testis, whereas one band at 70 kDa in epididymal sperm. pCABS1 immunoreactivity in seminiferous tubules was detected in the elongated spermatids, and that in the epididymal sperm was found in the acrosome as well as flagellum. The immunoreactivity of pCABS1 in the acrosomai region disappeared during acrosome reaction. We also identified that pCABS1 has a transmembrane domain using computational prediction of the amino acids sequence. The treatment of porcine capacitated sperm with anti-pCABS1 antiserum significantly decreased acrosome reactions. These results suggest that pCABS1 plays an important role in controlling calcium ion signaling during the acrosome reaction.
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http://dx.doi.org/10.1538/expanim.15-0104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976239PMC
July 2016

β-Cell-Specific Mafk Overexpression Impairs Pancreatic Endocrine Cell Development.

PLoS One 2016 22;11(2):e0150010. Epub 2016 Feb 22.

Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

The MAF family transcription factors are homologs of v-Maf, the oncogenic component of the avian retrovirus AS42. They are subdivided into 2 groups, small and large MAF proteins, according to their structure, function, and molecular size. MAFK is a member of the small MAF family and acts as a dominant negative form of large MAFs. In previous research we generated transgenic mice that overexpress MAFK in order to suppress the function of large MAF proteins in pancreatic β-cells. These mice developed hyperglycemia in adulthood due to impairment of glucose-stimulated insulin secretion. The aim of the current study is to examine the effects of β-cell-specific Mafk overexpression in endocrine cell development. The developing islets of Mafk-transgenic embryos appeared to be disorganized with an inversion of total numbers of insulin+ and glucagon+ cells due to reduced β-cell proliferation. Gene expression analysis by quantitative RT-PCR revealed decreased levels of β-cell-related genes whose expressions are known to be controlled by large MAF proteins. Additionally, these changes were accompanied with a significant increase in key β-cell transcription factors likely due to compensatory mechanisms that might have been activated in response to the β-cell loss. Finally, microarray comparison of gene expression profiles between wild-type and transgenic pancreata revealed alteration of some uncharacterized genes including Pcbd1, Fam132a, Cryba2, and Npy, which might play important roles during pancreatic endocrine development. Taken together, these results suggest that Mafk overexpression impairs endocrine development through a regulation of numerous β-cell-related genes. The microarray analysis provided a unique data set of differentially expressed genes that might contribute to a better understanding of the molecular basis that governs the development and function of endocrine pancreas.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0150010PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4763111PMC
July 2016
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