26,460 results match your criteria Biochemical Pharmacology[Journal]


Functional characterization of AC5 gain-of-function variants: Impact on the molecular basis of ADCY5-related dyskinesia.

Biochem Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Purdue University, Medicinal Chemistry and Molecular Pharmacology, 575 Stadium Mall Drive, West Lafayette, IN, 47907; Purdue Institute for Integrative Neuroscience, Hall for Discovery Learning - #399, 207 South Martin Jischke Drive, West Lafayette, IN. 47907; Purdue Institute for Drug Discovery, 720 Clinic Drive, West Lafayette, IN. 47907. Electronic address:

Adenylyl cyclases are key points for the integration of stimulatory and inhibitory G protein-coupled receptor (GPCR) signals. Adenylyl cyclase type 5 (AC5) is highly expressed in striatal medium spiny neurons (MSNs), and is known to play an important role in mediating striatal dopaminergic signaling. Dopaminergic signaling from the D expressing MSNs of the direct pathway, as well as the D expressing MSNs of the indirect pathway both function through the regulation of AC5 activity, controlling the production of the 2 messenger cAMP, and subsequently the downstream effectors. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.005DOI Listing
February 2019

The novel hybrid agonist HyNDA-1 targets the D3R-nAChR heteromeric complex in dopaminergic neurons.

Biochem Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Dipartimento di Scienze Farmaceutiche - Sezione di Chimica Farmaceutica "Pietro Pratesi", Università degli Studi di Milano, Via L. Mangiagalli 25, 20133 Milano, Italy. Electronic address:

In this paper, we designed, synthesized and tested a small set of three new derivatives potentially targeting the D3R-nAChR heteromer, a receptor complex recently identified and characterized as the molecular entity that, in dopaminergic neurons, mediates the neurotrophic effects of nicotine. By means of a partially rigidified spacer of variable length, we incorporated in the new compounds (1a-c) the pharmacophoric substructure of a known β2-subunit-containing nAChR agonist (A-84543) and that of the D2/D3R agonist drug ropinirole. All the compounds retained the ability to bind with high affinity both β2-subunit-containing nAChR and D3R. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.019DOI Listing
February 2019

Palbociclib triggers apoptosis in bladder cancer cells by Cdk2-induced Rad9-mediated reorganization of the Bak.Bcl-xl complex.

Biochem Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Medical School and State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China. Electronic address:

Palbociclib is a Cdk4/6 inhibitor approved for metastatic estrogen receptor-positive breast cancer. The drug is also under clinical evaluation for metastatic urothelial cancer and other solid tumors. Preclinical studies from multiple tumor types suggest that other factors also affect the sensitivity of individual tumors to Cdk4/6 inhibitor. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.017DOI Listing
February 2019

The role of the Hint1 protein in the metabolism of phosphorothioate oligonucleotides drugs and prodrugs, and the release of HS under cellular conditions.

Biochem Pharmacol 2019 Feb 14. Epub 2019 Feb 14.

Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, 91-063, Poland.

Phosphorothioate oligonucleotides (PS-oligos) containing sulfur atom attached in a nonbridging position to the phosphorus atom at one or more internucleotide bond(s) are often used in medicinal applications. Their hydrolysis in cellular media proceeds mainly from the 3'-end, resulting in the appearance of nucleoside 5'-O-phosphorothioates ((d)NMPS), whose further metabolism is poorly understood. We hypothesize that the enzyme responsible for (d)NMPS catabolism could be Hint1, an enzyme that belongs to the histidine triad (HIT) superfamily and is present in all organisms. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.018DOI Listing
February 2019

Characterization of aspirin esterase activity in health and disease: in vitro and ex vivo studies.

Biochem Pharmacol 2019 Feb 13. Epub 2019 Feb 13.

Centro Cardiologico Monzino, IRCCS, Milan, Italy.

Due to its ability to irreversibly inactivate platelet cyclooxygenase, low-dose aspirin (ASA) is the most widely used antithrombotic agent. Although, studies in specific types of patients with cardiovascular disease (CVD) have shown an incomplete inhibition of platelet's cyclooxygenase, which may increase the variability in drug response. Some aspects of ASA pharmacokinetics (PK) still need further investigation. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.014DOI Listing
February 2019

Nox2-mediated platelet activation by glycoprotein (GP) VI: effect of rivaroxaban alone and in combination with aspirin.

Biochem Pharmacol 2019 Feb 13. Epub 2019 Feb 13.

Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy. Electronic address:

Factor Xa (FXa) has been reported to activate platelet via interaction with glycoprotein (GP) VI but the underlying mechanism has not been fully elucidated. We investigated if Nox2-derived oxidative stress is implicated in FXa-induced platelet aggregation (PA), and the effect of a FXa inhibitor, namely rivaroxaban, with or without aspirin (ASA), on PA. We performed an in vitro study measuring convulxin-induced PA, thromboxane (Tx) B and isoprostanes biosynthesis, soluble Nox2-dp (sNox2-dp), a marker of Nox2 activation, soluble GPVI (sGPVI) and PLA activation in platelets from healthy subjects (n=5) added with and without a Nox2 inhibitor. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.016DOI Listing
February 2019

Alkylphenol inverse agonists of HCN1 gating: H-bond propensity, ring saturation and adduct geometry differentially determine efficacy and potency.

Biochem Pharmacol 2019 Feb 12. Epub 2019 Feb 12.

Weill Cornell Medicine, New York, NY, United States.

Background And Purpose: In models of neuropathic pain, inhibition of HCN1 is anti-hyperalgesic. 2,6-di-iso-propyl phenol (propofol) and its non-anesthetic congener, 2,6-di-tert-butyl phenol, inhibit HCN1 channels by stabilizing closed state(s).

Experimental: approach Using in vitro electrophysiology and kinetic modeling, we systematically explore the contribution of ligand architecture to alkylphenol-channel coupling. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.013DOI Listing
February 2019

Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle.

Biochem Pharmacol 2019 Feb 9. Epub 2019 Feb 9.

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, 77550, USA. Electronic address:

Aging is accompanied by progressive declines in skeletal muscle mass and strength and impaired regenerative capacity, predisposing older adults to debilitating age-related muscle deteriorations and severe morbidity. Muscle stem cells (muSCs) that proliferate, differentiate to fusion-competent myoblasts, and facilitate muscle regeneration are increasingly dysfunctional upon aging, impairing muscle recovery after injury. While regulators of muSC activity can offer novel therapeutics to improve recovery and reduce morbidity among aged adults, there are no known muSC regenerative small molecule therapeutics. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.008DOI Listing
February 2019

A novel soluble guanylyl cyclase activator, BR11257, acts as a non-stabilising partial agonist of sGC.

Biochem Pharmacol 2019 Feb 9. Epub 2019 Feb 9.

Department of Pharmacology, Toxicology and Clinical Pharmacy, University of Braunschweig - Institute of Technology, Germany. Electronic address:

The soluble guanylyl cyclase (sGC) plays a key role in NO/cGMP signalling and is widely recognised to be important in different disease pathomechanisms. The discovery of sGC agonists provides a new opportunity to stimulate the NO/cGMP pathway. One class of compounds are the heme-independent sGC activators, which are thought to bind to oxidised or heme-free sGC. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.007DOI Listing
February 2019

Time-dependent course of gastric ulcer healing and molecular markers profile modulated by increased gastric mucosal content of carbon monoxide released from its pharmacological donor.

Biochem Pharmacol 2019 Feb 10;163:71-83. Epub 2019 Feb 10.

Department of Physiology, Jagiellonian University Medical College, 16 Grzegorzecka Street, 31-531 Cracow, Poland. Electronic address:

Background And Purpose: Besides hydrogen sulfide (HS) and nitric oxide (NO), carbon monoxide (CO) contributes to the maintenance of gastric mucosal integrity. We investigated increased CO bioavailability effects on time-dependent dynamics of gastric ulcer healing mediated by particular growth factors, anti-inflammatory and molecular pathways.

Experimental Approach: Wistar rats with gastric ulcers induced by serosal acetic acid application (day 0) were treated i. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193004
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http://dx.doi.org/10.1016/j.bcp.2019.02.011DOI Listing
February 2019
1 Read

Impairment of chemical hypoxia-induced sphingosine kinase-1 expression and activation in rheumatoid arthritis synovial fibroblasts: A signature of exhaustion?

Biochem Pharmacol 2019 Feb 9. Epub 2019 Feb 9.

Centre de Recherche du Centre Hospitalier Universitaire de Québec - Université Laval, Département de microbiologie, infectiologie et immunologie, Faculté de Médecine, Université Laval, Québec, QC, G1V 4G2, Canada. Electronic address:

Sphingosine kinase 1 (SphK1) and 2 (SphK2) have been shown contribute to synovial inflammation in animal models of arthritis. However, low levels of intracellular sphingosine-1 phosphate (S1P) were reported in fibroblast-like synoviocytes (FLS) from patients in the end stage of rheumatoid arthritis (RA) compared to normal FLS. Moreover, the S1P receptor-mediated chemokine synthesis was altered in RAFLS in response to chemical hypoxia. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.009DOI Listing
February 2019
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Piperlongumine-induced nuclear translocation of the FOXO3A transcription factor triggers BIM-mediated apoptosis in cancer cells.

Biochem Pharmacol 2019 Feb 9. Epub 2019 Feb 9.

School of Biotechnology, Tianjin University of Science and Technology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin 300457, China. Electronic address:

The transcription factor forkhead box O 3A (FOXO3A) is a tumor suppressor that promotes cell cycle arrest and apoptosis. Piperlongumine (PL), a plant alkaloid, is known to selectively kill tumor cells while sparing normal cells. However, the mechanism of PL-induced cancer cell death is not fully understood. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.012DOI Listing
February 2019
2 Reads

AMPK: A promising molecular target for combating cisplatin toxicities.

Biochem Pharmacol 2019 Feb 7;163:94-100. Epub 2019 Feb 7.

Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Cisplatin is a broadly prescribed anti-tumor agent for the treatment of diverse cancers. Therapy with cisplatin, however, is associated with various adverse effects including nephrotoxicity and ototoxicity. AMP kinase (AMPK), an evolutionarily conserved enzyme, functions as the fundamental regulator of energy homeostasis. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193004
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http://dx.doi.org/10.1016/j.bcp.2019.02.006DOI Listing
February 2019
3 Reads
5.009 Impact Factor

7,8-Dihydroxyflavone blocks the development of behavioral sensitization to MDPV, but not to cocaine: Differential role of the BDNF-TrkB pathway.

Biochem Pharmacol 2019 Feb 6;163:84-93. Epub 2019 Feb 6.

Department of Pharmacology and Therapeutic Chemistry, Pharmacology Section and Institute of Biomedicine (IBUB), Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. Electronic address:

3,4-Methylenedioxypyrovalerone (MDPV) acts as a dopamine transporter blocker and exerts powerful psychostimulant effects. In this study we aimed to investigate the bidirectional cross-sensitization between MDPV and cocaine, as well as to evaluate the role of the BDNF-TrkB signaling pathway in the development of locomotor sensitization to both drugs. Mice were treated with MDPV (1. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.004DOI Listing
February 2019

Helicobacter pylori infection promotes autophagy through Nrf2-mediated heme oxygenase upregulation in human gastric cancer cells.

Biochem Pharmacol 2019 Feb 4. Epub 2019 Feb 4.

Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, South Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Sciences and Technology, Seoul National University, Seoul 08826, South Korea; Cancer Research Institute, Seoul National University, Seoul 03080, South Korea. Electronic address:

It has been reported that Helicobacter pylori (H. pylori) infection is one of the primary causes of gastritis and peptic ulcer diseases. More than 50% of the world's population is supposed to be infected by this bacterium. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.003DOI Listing
February 2019
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Dehydrocostus lactone (DHC) Suppresses Estrogen Deficiency-Induced Osteoporosis.

Biochem Pharmacol 2019 Feb 2. Epub 2019 Feb 2.

Department of Orthopedics, The Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, 515041, China. Electronic address:

Osteoporosis is a chronic bone lytic disease, because of inadequate bone ossification and/or excessive bone resorption. Even though drugs are currently available for the treatment of osteoporosis, there remains an unmet need for the development of more specific novel agents with less adverse effects. Dehydrocostus lactone (DHC), a natural sesquiterpene lactone, was previously found to affect the differentiation of inflammatory cells by the inhibiting NF-κB pathways, and garnered much interest for its anti-cancer properties via SOCS-mediated cell cycle arrest and apoptosis. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.02.002DOI Listing
February 2019
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Transport of ribavirin across the rat and human placental barrier: Roles of nucleoside and ATP-binding cassette drug efflux transporters.

Biochem Pharmacol 2019 Feb 2;163:60-70. Epub 2019 Feb 2.

Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Czech Republic. Electronic address:

Ribavirin is a broad-spectrum nucleoside-derived antiviral drug used in combination pharmacotherapy treatment of hepatitis C virus infection. Current evidence indicates that ribavirin-associated teratogenicity is not significant in humans, but more information about the developmental toxicity and mechanisms involved in ribavirin placental kinetics is required to assure its safe use in pregnancy. Thus, we have investigated potential roles of equilibrative nucleoside transporters (ENTs, SLC29A), Na-dependent influx-mediating concentrative nucleoside transporters (CNTs, SLC28A), and ATP-binding cassette (ABC) efflux pumps, in ribavirin placental pharmacokinetics. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.024DOI Listing
February 2019
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Ability of CP-532,903 to protect mouse hearts from ischemia/reperfusion injury is dependent on expression of A adenosine receptors in cardiomyoyctes.

Biochem Pharmacol 2019 Jan 30;163:21-31. Epub 2019 Jan 30.

Department of Pharmacology & Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, United States; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, United States. Electronic address:

A adenosine receptor (AAR) agonists are effective at limiting injury caused by ischemia/reperfusion injury of the heart in experimental animal models. However, understanding of their mechanism of action, which is likely multifactorial, remains incomplete. In prior studies, it has been demonstrated that AAR-mediated ischemic protection is blocked by glibenclamide and is absent in Kir6. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.022DOI Listing
January 2019

Benproperine, an ARPC2 inhibitor, suppresses cancer cell migration and tumor metastasis.

Biochem Pharmacol 2019 Jan 30;163:46-59. Epub 2019 Jan 30.

Laboratory of Chemical Biology and Genomics, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahakro, Daejeon 34141, Republic of Korea; Korea University of Science and Technology in Korea, Daejeon, Republic of Korea. Electronic address:

Metastasis is the leading cause of cancer mortality and cancer cell migration is an essential stage of metastasis. We identified benproperine (Benp, a clinically used antitussive drug) as an inhibitor of cancer cell migration and an anti-metastatic agent. Benp selectively inhibited cancer cell migration and invasion, which also suppressed metastasis of cancer cells in animal models. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193002
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http://dx.doi.org/10.1016/j.bcp.2019.01.017DOI Listing
January 2019
1 Read
5.009 Impact Factor

Crocin, a carotenoid, suppresses spindle microtubule dynamics and activates the mitotic checkpoint by binding to tubulin.

Biochem Pharmacol 2019 Jan 30;163:32-45. Epub 2019 Jan 30.

Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India. Electronic address:

Crocin, a constituent of the saffron spice, exhibits promising antitumor activity in animal models and also inhibits the proliferation of several types of cancer cells in culture. Recently, we have shown that crocin binds to purified tubulin at the vinblastine site, depolymerizes microtubules and induces a mitotic block in cultured cells. Here, we extend our previous suggestion and explore the cellular effects of crocin to further understand its mechanism of action. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193002
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http://dx.doi.org/10.1016/j.bcp.2019.01.023DOI Listing
January 2019
2 Reads

Paricalcitol alleviates lipopolysaccharide-induced depressive-like behavior by suppressing hypothalamic microglia activation and neuroinflammation.

Biochem Pharmacol 2019 Jan 28;163:1-8. Epub 2019 Jan 28.

Spine Disease Research Institute, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Key Laboratory (Theory and Therapy of Muscles and Bones) of Ministry of Education, Shanghai 200032, China. Electronic address:

Depression is highly prevalent in patients suffering from chronic inflammatory diseases. Dysregulated neuroinflammation and concomitant activated microglia play a pivotal role in the pathogenesis of depression. Paricalcitol (Pari), a vitamin D2 analogue, has been demonstrated to exert anti-inflammative effects on renal and cardiovascular diseases. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.021DOI Listing
January 2019
1 Read

Mining the Na1.7 interactome: Opportunities for chronic pain therapeutics.

Biochem Pharmacol 2019 Jan 27;163:9-20. Epub 2019 Jan 27.

Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA; Graduate Interdisciplinary Program in Neuroscience, College of Medicine, University of Arizona, Tucson, AZ, USA; The Center for Innovation in Brain Sciences, The University of Arizona Health Sciences, Tucson, AZ 85724, USA. Electronic address:

The peripherally expressed voltage-gated sodium Na1.7 (gene SCN9A) channel boosts small stimuli to initiate firing of pain-signaling dorsal root ganglia (DRG) neurons and facilitates neurotransmitter release at the first synapse within the spinal cord. Mutations in SCN9A produce distinct human pain syndromes. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.018DOI Listing
January 2019

The nuclear receptor Shp regulates morphine withdrawal syndrome via modulation of Ugt2b expression in mice.

Biochem Pharmacol 2019 Mar 25;161:163-172. Epub 2019 Jan 25.

Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, China. Electronic address:

In this study, we aimed to investigate a potential role of small heterodimer partner (Shp, a nuclear receptor) in regulation of morphine withdrawal syndrome and to determine the mechanisms thereof. Somatic opiate withdrawal and pharmacokinetic experiments were performed with wild-type (WT) and Shp knockout (Shp-KO) mice. Regulatory effects of Shp on Ugt2b expression were assessed in vitro (using mouse hepatoma Hepa1-6 cells) and in vivo (using Shp-KO mice). Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193002
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http://dx.doi.org/10.1016/j.bcp.2019.01.019DOI Listing
March 2019
3 Reads

Understanding the cancer stem cell phenotype: A step forward in the therapeutic management of cancer.

Biochem Pharmacol 2019 Jan 25. Epub 2019 Jan 25.

Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Medical Science Cluster Cancer Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; National University Cancer Institute, National University Health System, Singapore, Singapore; NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore. Electronic address:

The experimental validation of the existence of cancer stem cells (CSC) has had a significant impact on our understanding of the cellular mechanisms and signaling networks involved in the process of carcinogenesis and its progression. These findings provide insights into the critical role that tumor microenvironment and metabolism play in the acquisition of the drug resistance phenotype as well as provide potential targets for therapeutic exploitation. Here we briefly review the literature on the involvement of key signaling pathways such as Wnt/β-catenin, Notch, Hedgehog and STAT3 in the appearance of cancer cells with stem cells-like characteristics. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.020DOI Listing
January 2019

Betulinic acid suppresses breast cancer aerobic glycolysis via caveolin-1/NF-κB/c-Myc pathway.

Biochem Pharmacol 2019 Mar 24;161:149-162. Epub 2019 Jan 24.

Integrative Research Laboratory of Breast Cancer, Discipline of Integrated Chinese and Western Medicine, the Research Center of Integrative Medicine, School of Basic Medical Sciences & the Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangdong Provincial Academy of Chinese Medical Sciences, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China; Post-doctoral Research Center, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China. Electronic address:

Emerging evidence has suggested that targeting glycolysis may be a promising strategy for cancer treatment. Betulinic acid (BA) is a natural pentacyclic terpene that has been reported to be active in inhibiting various malignancies. Here, we showed that BA could inhibit aerobic glycolysis activity in breast cancer cell lines MCF-7 and MDA-MB-231 by hampering lactate production, glucose uptake and extracellular acidification rate (ECAR), as well as suppressing aerobic glycolysis-related proteins including c-Myc, lactate dehydrogenase A (LDH-A) and p-PDK1/PDK1 (pyruvate dehydrogenase kinase 1). Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.016DOI Listing

Gelsemine and koumine, principal active ingredients of Gelsemium, exhibit mechanical antiallodynia via spinal glycine receptor activation-induced allopregnanolone biosynthesis.

Biochem Pharmacol 2019 Mar 19;161:136-148. Epub 2019 Jan 19.

King's Lab, Shanghai Jiao Tong University School of Pharmacy, 800 Dongchuan Road, Shanghai 200240, China. Electronic address:

Gelsemine, the principal active alkaloid from Gelsemium sempervirens Ait., and koumine, the most dominant alkaloids from Gelsemium elegans Benth., produced antinociception in a variety of rodent models of painful hypersensitivity. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.014DOI Listing
March 2019
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A delicate balance - The BCL-2 family and its role in apoptosis, oncogenesis, and cancer therapeutics.

Biochem Pharmacol 2019 Jan 19. Epub 2019 Jan 19.

Department of Pediatrics, Wayne State University School of Medicine, Detroit, MI, USA; Cancer Biology Graduate Program, Wayne State University School of Medicine, Detroit, MI, USA; Department of Oncology, Wayne State University School of Medicine, Detroit, MI, USA; Molecular Therapeutics Program, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address:

Evasion of apoptosis is fundamental to the pathogenesis of cancer. Members of the B-cell Lymphoma 2 (BCL-2) protein family are key pro- and anti-apoptotic regulators, and in healthy cells are held in a fine, delicate balance - perturbations of which may tip a cell irreversibly towards cellular death or, conversely, allow a cell to permanently escape apoptosis and immortalize itself as a malignant clone. The restoration of this balance or, indeed, adjustment in favor of apoptosis via manipulation of the BCL-2 family, is a promising area in the realm of molecular therapeutics, and one in which breathtaking advances are currently being made. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.015DOI Listing
January 2019

Targeting intrinsic cell death pathways to control fungal pathogens.

Biochem Pharmacol 2019 Jan 17. Epub 2019 Jan 17.

Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, USA. Electronic address:

Fungal pathogens pose an increasing threat to public health. Limited clinical drug regimens and emerging drug-resistant isolates challenge infection control. The global burden of human fungal pathogens is estimated at 1 billion infections and 1. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.012DOI Listing
January 2019
1 Read

New tricks of prolyl oligopeptidase inhibitors - A common drug therapy for several neurodegenerative diseases.

Biochem Pharmacol 2019 Mar 17;161:113-120. Epub 2019 Jan 17.

Division of Pharmacology and Pharmacotherapy, Drug Research Program, Faculty of Pharmacy, Viikinkaari 5E (PO Box 56), 00014 University of Helsinki, Finland. Electronic address:

Changes in prolyl oligopeptidase (PREP) expression levels, protein distribution, and activity correlate with aging and are reported in many neurodegenerative conditions. Together with decreased neuropeptide levels observed in aging and neurodegeneration, and PREP's ability to cleave only small peptides, PREP was identified as a druggable target. Known PREP non-enzymatic functions were disregarded or attributed to PREP enzymatic activity, and several potent small molecule PREP inhibitors were developed during early stages of PREP research. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193001
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http://dx.doi.org/10.1016/j.bcp.2019.01.013DOI Listing
March 2019
4 Reads

Non-immunological toxicological mechanisms of metamizole-associated neutropenia in HL60 cells.

Biochem Pharmacol 2019 Jan 14. Epub 2019 Jan 14.

Division of Clinical Pharmacology & Toxicology, University Hospital, Basel, Switzerland; Department of Biomedicine, University of Basel, Switzerland; Swiss Centre of Applied Human Toxicology (SCAHT), Basel, Switzerland. Electronic address:

Metamizole is an analgesic and antipyretic, but can cause neutropenia and agranulocytosis. We investigated the toxicity of the metabolites N-methyl-4-aminoantipyrine (MAA), 4-aminoantipyrine (AA), N-formyl-4-aminoantipyrine (FAA) and N-acetyl-4-aminoantipyrine (AAA) on neutrophil granulocytes and on HL60 cells (granulocyte precursor cell line). MAA, FAA, AA, and AAA (up to 100 µM) alone were not toxic for HL60 cells or granulocytes. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.011DOI Listing
January 2019
2 Reads

Structural optimization and anti-allergic activity of nucleotide aptamers target to Cε3-Cε4.

Biochem Pharmacol 2019 Mar 14;161:121-135. Epub 2019 Jan 14.

College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China; Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Baoding 071002, China. Electronic address:

Nucleic acid aptamers have shown a broad application prospect in basic research, clinical diagnosis and treatment, new drug development and various other fields. We have screened the DNA aptamer A1 and A2 target at Cε3-Cε4 with high affinity and specificity, another aptamer A8, no affinity with Cε3-Cε4 protein, was as a negative control in this study. The structures of aptamer A1 and A2 were optimized using the deletion method, complementary sequence method, and point mutation method, to make them perform biological functions better, improve the pertinence of the subsequent modification and study the mechanism of action of aptamers coupled Cε3-Cε4. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.008DOI Listing
March 2019
6 Reads

miR-142-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes.

Biochem Pharmacol 2019 Mar 11;161:98-112. Epub 2019 Jan 11.

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, China. Electronic address:

Chemotherapy is the preferred treatment for advanced ovarian cancer, but the 5-year survival rate remains low partly because of the development of drug resistance. Although it has been reported that X-linked inhibitor of apoptosis (XIAP) causes more severe chemoresistance in ovarian cancer cells and is highly expressed in chemoresistant ovarian cancer, the molecular mechanism underlying this dysregulation is unknown. The purpose of this study was to identify microRNAs (miRNAs) that bind to the 3' untranslated region (3'UTR) of XIAP and have a role in chemoresistance in ovarian cancer. Read More

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https://linkinghub.elsevier.com/retrieve/pii/S00062952193001
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http://dx.doi.org/10.1016/j.bcp.2019.01.009DOI Listing
March 2019
5 Reads

The nuclear receptor Rev-erbα participates in circadian regulation of Ugt2b enzymes in mice.

Biochem Pharmacol 2019 Mar 11;161:89-97. Epub 2019 Jan 11.

Research Center for Biopharmaceutics and Pharmacokinetics, College of Pharmacy, Jinan University, 601 Huangpu Avenue West, Guangzhou, China. Electronic address:

Circadian clock is known to modulate phase I metabolism, however whether and how the phase II enzymes UDP-glucuronosyltransferases (UGTs) are regulated by circadian clock are largely unknown. In this study, we aimed to investigate a potential role of the clock gene Rev-erbα in regulation of Ugt2b enzymes. Ugt2b mRNA and protein expression in mouse livers were determined at a 4-h interval around the clock. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.010DOI Listing
March 2019
5 Reads

Anti-tumor effect of sulfasalazine in neuroblastoma.

Biochem Pharmacol 2019 Jan 9. Epub 2019 Jan 9.

Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, 400 Monroe Ave NW, Grand Rapids, MI 49503, USA. Electronic address:

Neuroblastoma (NB) is a tumor arising from the sympathetic nervous system during infancy and early childhood. High-risk patients who relapse often fail to respond to further therapy, which results in 5-year survival rate for this patient group below 5%. Therefore, there continues to be an urgent need for innovative treatments. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.007DOI Listing
January 2019
7 Reads
5.009 Impact Factor

SARM: From immune regulator to cell executioner.

Biochem Pharmacol 2019 Mar 8;161:52-62. Epub 2019 Jan 8.

School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.

SARM is the fifth and most conserved member of the Toll/Il-1 Receptor (TIR) adaptor family. However, unlike the other TIR adaptors, MyD88, Mal, TRIF and TRAM, SARM does not participate in transducing signals downstream of TLRs. By contrast SARM inhibits TLR signalling by interacting with the adaptors TRIF and MyD88. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.005DOI Listing
March 2019
5 Reads

Growth of breast cancer cells by leptin is mediated via activation of the inflammasome: Critical roles of estrogen receptor signaling and reactive oxygen species production.

Biochem Pharmacol 2019 Mar 10;161:73-88. Epub 2019 Jan 10.

College of Pharmacy, Yeungnam University, Gyeongsan, Republic of Korea. Electronic address:

Leptin, a hormone primarily derived from adipose tissue, is known to induce tumor growth, but its underlying mechanisms of action are not clearly understood. Inflammasomes, acting as signaling platforms for controlling inflammatory responses, modulate tumor growth in a complicated manner. In this study, we investigated the role of inflammasomes in leptin-induced growth of breast cancer cells. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.006DOI Listing
March 2019
7 Reads

Potentialization of anticancer agents by identification of new chemosensitizers active under hypoxia.

Biochem Pharmacol 2019 Jan 7. Epub 2019 Jan 7.

URBC - NARILIS, University of Namur, 61 rue de Bruxelles, Namur, Belgium. Electronic address:

Hypoxia is one of the most important biological phenomena that influences cancer agressiveness and chemotherapy resistance. Cancer cells display dysregulated pathways notably resulting from oncogene expression. Tumors also show modifications in extracellular pH, extracellular matrix remodeling, neo-angiogenesis, hypoxia compared to normal tissues. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.004DOI Listing
January 2019
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5.009 Impact Factor

Involvement of cell oxidant status and redox state in the increased non-enzymatic ethanol oxidation by the regenerating rat liver.

Biochem Pharmacol 2019 Mar 6;161:63-72. Epub 2019 Jan 6.

Departamento de Biología Celular y Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Apdo. Postal 70-245, Mexico City 04510, Mexico.

Ethanol administration is capable of inhibiting or delaying the partial hepatectomy (PH)-induced liver regeneration, probably altering liver metabolism by means of its oxidative metabolism. Since the regenerating liver has increased capacity for oxidizing ethanol, the present study was aimed to address the contribution of the ethanol-oxidizing metabolic pathways in the regenerating liver cells. Isolated hepatocytes were prepared from control livers and from animals subjected to two-thirds PH. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.003DOI Listing
March 2019
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Natural modulators of the hallmarks of immunogenic cell death.

Biochem Pharmacol 2019 Jan 5. Epub 2019 Jan 5.

College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, South Korea. Electronic address:

Natural compounds act as immunoadjuvants as their therapeutic effects trigger cancer stress response and release of damage-associated molecular patterns (DAMPs). These reactions occur through an increase in the immunogenicity of cancer cells that undergo stress followed by immunogenic cell death (ICD). These processes result in a chemotherapeutic response with a potent immune-mediating reaction. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.016DOI Listing
January 2019
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Calcineurin/P38MAPK/HSP27-dependent pathways are involved in the attenuation of postischemic mitochondrial injury afforded by sodium bicarbonate co-transporter (NBCe1) inhibition.

Biochem Pharmacol 2019 Mar 4;161:26-36. Epub 2019 Jan 4.

Centro de Investigaciones Cardiovasculares Dr Horacio E Cingolani, CCT-CONICET, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Buenos Aires, Argentina. Electronic address:

The electrogenic sodium bicarbonate co-transporter isoform 1 (NBCe1) plays an important role in ischemia-reperfusion injury. The cardioprotective action of an antibody directed to the extracellular loop 3 (a-L3) of NBCe1 was previously demonstrated by us. However, the role of a-L3 on mitochondrial post-ischemic alterations has not yet been determined. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.002DOI Listing
March 2019
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Systemic administration of serotonin exacerbates abdominal pain and colitis via interaction with the endocannabinoid system.

Biochem Pharmacol 2019 Mar 3;161:37-51. Epub 2019 Jan 3.

Department Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland. Electronic address:

Background And Aims: Molecular basis of abdominal pain in IBD is not fully characterized. Serotonin (5-HT) increases visceral pain severity and contributes to exacerbation of inflammation. Moreover, it is well established that decreased anandamide (AEA) signaling in the gut increases visceral pain severity. Read More

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http://dx.doi.org/10.1016/j.bcp.2019.01.001DOI Listing
March 2019
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Developments in bile salt based therapies: A critical overview.

Biochem Pharmacol 2019 Mar 22;161:1-13. Epub 2018 Dec 22.

Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology and Metabolism, Amsterdam, the Netherlands; Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Amsterdam Gastroenterology and Metabolism, Amsterdam, the Netherlands. Electronic address:

Bile acids, amphipathic molecules known for their facilitating role in fat absorption, are also recognized as signalling molecules acting via nuclear and membrane receptors. Of the bile acid-activated receptors, the Farnesoid X Receptor (FXR) and the G protein-coupled bile acid receptor-1 (Gpbar1 or TGR5) have been studied most extensively. Bile acid signaling is critical in the regulation of bile acid metabolism itself, but it also plays a significant role in glucose, lipid and energy metabolism. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.018DOI Listing
March 2019
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Schedule-dependent synergistic effects of 5-fluorouracil and selumetinib in KRAS or BRAF mutant colon cancer models.

Biochem Pharmacol 2019 Feb 21;160:110-120. Epub 2018 Dec 21.

Department of Nuclear Medicine, Asan Medical Center, University of Ulsan, College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Republic of Korea. Electronic address:

Combination of MEK inhibitor and 5-FU had showed limited efficacy in clinical trials. We previously reported that acquired resistance to 5-FU was related with continued activation of salvage pathway. Here we investigated whether combination of 5-FU and a MEK inhibitor had treatment sequence-dependent synergistic effects in KRAS or BRAF mutant colon cancer models. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.017DOI Listing
February 2019
2 Reads

An N-methyladenosine at the transited codon 273 of p53 pre-mRNA promotes the expression of R273H mutant protein and drug resistance of cancer cells.

Biochem Pharmacol 2019 Feb 19;160:134-145. Epub 2018 Dec 19.

School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana at Monroe, Monroe, LA 71201, USA. Electronic address:

Mutant p53 proteins that promote cancer cell invasive growth, metastasis and drug resistance emerge as therapeutic targets. Previously, we reported that suppression of ceramide glycosylation restored wild-type p53 protein and tumor suppressing function in cancer cells heterozygously carrying p53 R273H, a hot-spot missense mutation; however, the mechanisms underlying the control of mutant protein expression remain elusive. Herein, we report that an N-methyladenosine (mA) at the point-mutated codon 273 (G > A) of p53 pre-mRNA determines the mutant protein expression. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.014DOI Listing
February 2019
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5.009 Impact Factor

Contrasting effects of microtubule destabilizers versus stabilizers on induction of death in G1 phase of the cell cycle.

Biochem Pharmacol 2018 Dec 19. Epub 2018 Dec 19.

Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, United States. Electronic address:

Microtubule targeting agents (MTAs) have been reported to manifest their cytotoxic effects not only in mitosis but also in interphase. However, the relationship between phase-specific susceptibility and MTA concentration, especially with respect to microtubule integrity, remains poorly defined. In addition, whether microtubule stabilizers and destabilizers act similarly or differ in the ability to induce interphase death is unclear. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.015DOI Listing
December 2018
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Tumor cell escape from therapy-induced senescence.

Biochem Pharmacol 2018 Dec 19. Epub 2018 Dec 19.

Departments of Pharmacology & Toxicology and Medicine, and Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States. Electronic address:

H460 non-small cell lung, HCT116 colon and 4T1 breast tumor cell lines induced into senescence by exposure to either etoposide or doxorubicin were able to recover proliferative capacity both in mass culture and when enriched for the senescence-like phenotype by flow cytometry (based on β-galactosidase staining and cell size, and a senescence-associated reporter, BTG1-RFP). Recovery was further established using both real-time microscopy and High-Speed Live-Cell Interferometry (HSLCI) and was shown to be accompanied by the attenuation of the Senescence-Associated Secretory Phenotype (SASP). Cells enriched for the senescence-like phenotype were also capable of forming tumors when implanted in both immunodeficient and immunocompetent mice. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.013DOI Listing
December 2018
8 Reads

RNA interference screen identifies NAA10 as a regulator of PXR transcription.

Biochem Pharmacol 2019 Feb 16;160:92-109. Epub 2018 Dec 16.

Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, TN 38105, United States; Integrated Biomedical Sciences Program, University of Tennessee Health Science Center, Memphis, TN 38163, United States. Electronic address:

The pregnane X receptor (PXR) is a principal xenobiotic receptor crucial in the detection, detoxification, and clearance of toxic substances from the body. PXR plays a vital role in the metabolism and disposition of drugs, and elevated PXR levels contribute to cancer drug resistance. Therefore, to modulate PXR activity and mitigate drug resistance, it is imperative to fully understand its regulation. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6361121PMC
February 2019
2 Reads
5.009 Impact Factor

Inositol hexakisphosphate increases the size of platelet aggregates.

Biochem Pharmacol 2019 Mar 14;161:14-25. Epub 2018 Dec 14.

Department of Biochemistry and Signal Transduction, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany. Electronic address:

The inositol phosphates, InsP and InsP, have recently been identified as binding partners of fibrinogen, which is critically involved in hemostasis by crosslinking activated platelets at sites of vascular injury. Here, we investigated the putative physiological role of this interaction and found that platelets increase their InsP concentration upon stimulation with the PLC-activating agonists thrombin, collagen I and ADP and present a fraction of it at the outer plasma membrane. Cone and plate analysis in whole blood revealed that InsP specifically increases platelet aggregate size. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6372069PMC
March 2019
10 Reads

Lung cancer stem cells: origin, features, maintenance mechanisms and therapeutic targeting.

Biochem Pharmacol 2019 Feb 14;160:121-133. Epub 2018 Dec 14.

Department of Medical Oncology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. Electronic address:

Lung cancer remains the leading cause of cancer-related deaths despite recent breakthroughs in immunotherapy. The widely embraced cancer stem cell (CSC) theory has also been applied for lung cancer, postulating that an often small proportion of tumor cells with stem cell properties are responsible for tumor growth, therapeutic resistance and metastasis. The identification of these CSCs and underlying molecular maintenance mechanisms is considered to be absolutely necessary for developing therapies for their riddance, hence achieving remission. Read More

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February 2019
6 Reads

Development of a novel, sensitive cell-based corin assay.

Biochem Pharmacol 2019 Feb 13;160:62-70. Epub 2018 Dec 13.

Lead Discovery Wuppertal, Bayer AG, Pharma Research and Development Center, Aprather Weg 18a, D-42096 Wuppertal, Germany. Electronic address:

Corin (atrial natriuretic peptide-converting enzyme, EC 3.4.21) is a transmembrane serine protease expressed in cardiomyocytes. Read More

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http://dx.doi.org/10.1016/j.bcp.2018.12.009DOI Listing
February 2019
11 Reads