Deletion of hepatocyte cysteine dioxygenase type 1, a bile acid repressed gene, enhances glutathione synthesis and ameliorates acetaminophen hepatotoxicity
Biochem Pharmacol. 2024 Feb 28:116103. doi: 10.1016/j.bcp.2024.116103. Online ahead of print.ABSTRACTLiver is a major organ that metabolizes sulfur amino acids cysteine, which is the substrate for the synthesis of many essential cellular molecules including GSH, taurine, and coenzyme A. Bile acid-activated farnesoid x receptor (FXR) inhibits cysteine dioxygenase type 1 (CDO1), which mediates hepatic cysteine catabolism and taurine synthesis. To define the impact of bile acid inhibition of CDO1 on hepatic sulfur amino acid metabolism and antioxidant capacity, we developed hepatocyte-specific CDO1 knockout mice (Hep-CDO1 KO)...
Source: Biochemical Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Authors: Jianglei Chen David Matye Yung Dai Clayton Yanhong Du Mohammad Nazmul Hasan Lijie Gu Tiangang Li Source Type: research
The role of novel adipokines and adipose-derived extracellular vesicles (ADEVs): Connections and interactions in liver diseases
Biochem Pharmacol. 2024 Feb 28:116104. doi: 10.1016/j.bcp.2024.116104. Online ahead of print.ABSTRACTAdipose tissues (AT) are an important endocrine organ that secretes various functional adipokines, peptides, non-coding RNAs, and acts on AT themselves or other distant tissues or organs through autocrine, paracrine, or endocrine manners. An accumulating body of evidence has suggested that many adipokines play an important role in liver metabolism. Besides the traditional adipokines such as adiponectin and leptin, many novel adipokines have recently been identified to have regulatory effects on the liver. Additionally, AT c...
Source: Biochemical Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Authors: Lijun Xie Huiying Wang Jinying Hu Zhuoying Liu Fang Hu Source Type: research
Proliferation and migration of PC-3 prostate cancer cells is counteracted by PPAR γ-cladosporol binding-mediated apoptosis and a decreased lipid biosynthesis and accumulation
CONCLUSION: This is the first work, to our knowledge, in which the role of cladosporols A and B was disclosed in prostate cancer cells. Importantly, the present study highlighted the potential of cladosporols as new therapeutical tools, which, interfering with cell proliferation and lipid pathway dysregulation, may control prostate cancer initiation and progression.PMID:38428827 | DOI:10.1016/j.bcp.2024.116097 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Authors: Roberta Rapuano Alessio Riccio Antonella Mercuri Jessica Raffaella Madera Sabrina Dallavalle Salvatore Moricca Angelo Lupo Source Type: research
STING deficiency alleviates ferroptosis through FPN1 stabilization in diabetic kidney disease
In conclusion, STING deficiency protected against diabetic renal injury via alleviating ferroptosis through stabilizing FPN1 and reducing oxidative stress, providing a possible potential approach for the treatment of DKD.PMID:38428828 | DOI:10.1016/j.bcp.2024.116102 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - March 1, 2024 Category: Drugs & Pharmacology Authors: Qin-Xiao Zhao Sen-Bo Yan Fen Wang Xiao-Xing Li Guo-Kai Shang Zi-Jie Zheng Jie Xiao Zong-Wei Lin Chuan-Bao Li Xiao-Ping Ji Source Type: research
PPAR γ antagonists induce aromatase transcription in adipose tissue cultures
This study aimed to test the hypothesis that PPARγ antagonists can promote breast cancer by stimulating aromatase expression in human adipose tissue. Primary cells and explants from human adipose tissue as well as A41hWAT, C3H10T1/2, and H295R cell lines were used to investigate PPARγ antagonist-stimulated effects on adipogenesis, aromatase expression, and estrogen biosynthesis. Selected antagonists inhibited adipocyte differentiation, preventing the adipogenesis-associated downregulation of aromatase. NMR spectroscopy confirmed direct interaction between the potent antagonist DEHPA and PPARγ, inhibiting agonist binding...
Source: Biochemical Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Authors: Jacob Ardenkj ær-Skinnerup Daniel Saar Patricia S S Petersen Mikael Pedersen Terje Svingen Birthe B Kragelund Niels Hadrup Gitte Ravn-Haren Brice Emanuelli Kristy A Brown Ulla Vogel Source Type: research
Quercetin protects cardiomyoblasts against hypertonic cytotoxicity by abolishing intracellular Ca < sup > 2+ < /sup > elevations and mitochondrial depolarisation
CONCLUSIONS AND IMPLICATIONS: Quercetin, but not 2,3-dehydrosilybin, reduced adverse effects of osmotic stress mainly by dampening the elevation of [Ca2+]cyto and mitochondrial Ca2+ overload. This may consequently prevent MPTP pore opening and activation of apoptosis.PMID:38423187 | DOI:10.1016/j.bcp.2024.116094 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Authors: Z Dost ál A V Zholobenko H P řichystalová B Gottschalk K Valentov á R Malli M Modriansk ý Source Type: research
Ca < sub > v < /sub > 3.1 T-type calcium channel blocker NNC 55-0396 reduces atherosclerosis by increasing cholesterol efflux
Biochem Pharmacol. 2024 Feb 27:116096. doi: 10.1016/j.bcp.2024.116096. Online ahead of print.ABSTRACTCalcium channel blockers (CCBs) are commonly used as antihypertensive agents. While certain L-type CCBs exhibit antiatherogenic effects, the impact of Cav3.1 T-type CCBs on antiatherogenesis and lipid metabolism remains unexplored. NNC 55-0396 (NNC) is a highly selective blocker of T-type calcium channels (Cav3.1 channels). We investigated the effects of NNC on relevant molecules and molecular mechanisms in human THP-1 macrophages. Cholesterol efflux, an indicator of reverse cholesterol transport (RCT) efficiency, was asses...
Source: Biochemical Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Authors: Min-Chien Tsai Rou-Ling Cho Chin-Sheng Lin Yu-Sin Jheng Chih-Feng Lien Chien-Chang Chen Bing-Hsiean Tzeng Source Type: research
PPAR γ antagonists induce aromatase transcription in adipose tissue cultures
This study aimed to test the hypothesis that PPARγ antagonists can promote breast cancer by stimulating aromatase expression in human adipose tissue. Primary cells and explants from human adipose tissue as well as A41hWAT, C3H10T1/2, and H295R cell lines were used to investigate PPARγ antagonist-stimulated effects on adipogenesis, aromatase expression, and estrogen biosynthesis. Selected antagonists inhibited adipocyte differentiation, preventing the adipogenesis-associated downregulation of aromatase. NMR spectroscopy confirmed direct interaction between the potent antagonist DEHPA and PPARγ, inhibiting agonist binding...
Source: Biochemical Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Authors: Jacob Ardenkj ær-Skinnerup Daniel Saar Patricia S S Petersen Mikael Pedersen Terje Svingen Birthe B Kragelund Niels Hadrup Gitte Ravn-Haren Brice Emanuelli Kristy A Brown Ulla Vogel Source Type: research
Quercetin protects cardiomyoblasts against hypertonic cytotoxicity by abolishing intracellular Ca < sup > 2+ < /sup > elevations and mitochondrial depolarisation
CONCLUSIONS AND IMPLICATIONS: Quercetin, but not 2,3-dehydrosilybin, reduced adverse effects of osmotic stress mainly by dampening the elevation of [Ca2+]cyto and mitochondrial Ca2+ overload. This may consequently prevent MPTP pore opening and activation of apoptosis.PMID:38423187 | DOI:10.1016/j.bcp.2024.116094 (Source: Biochemical Pharmacology)
Source: Biochemical Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Authors: Z Dost ál A V Zholobenko H P řichystalová B Gottschalk K Valentov á R Malli M Modriansk ý Source Type: research
Ca < sub > v < /sub > 3.1 T-type calcium channel blocker NNC 55-0396 reduces atherosclerosis by increasing cholesterol efflux
Biochem Pharmacol. 2024 Feb 27:116096. doi: 10.1016/j.bcp.2024.116096. Online ahead of print.ABSTRACTCalcium channel blockers (CCBs) are commonly used as antihypertensive agents. While certain L-type CCBs exhibit antiatherogenic effects, the impact of Cav3.1 T-type CCBs on antiatherogenesis and lipid metabolism remains unexplored. NNC 55-0396 (NNC) is a highly selective blocker of T-type calcium channels (Cav3.1 channels). We investigated the effects of NNC on relevant molecules and molecular mechanisms in human THP-1 macrophages. Cholesterol efflux, an indicator of reverse cholesterol transport (RCT) efficiency, was asses...
Source: Biochemical Pharmacology - February 29, 2024 Category: Drugs & Pharmacology Authors: Min-Chien Tsai Rou-Ling Cho Chin-Sheng Lin Yu-Sin Jheng Chih-Feng Lien Chien-Chang Chen Bing-Hsiean Tzeng Source Type: research
Finding new analgesics: Computational pharmacology faces drug discovery challenges
Biochem Pharmacol. 2024 Feb 25:116091. doi: 10.1016/j.bcp.2024.116091. Online ahead of print.ABSTRACTDespite the worldwide prevalence and huge burden of pain, pain is an undertreated phenomenon. Currently used analgesics have several limitations regarding their efficacy and safety. The discovery of analgesics possessing a novel mechanism of action has faced multiple challenges, including a limited understanding of biological processes underpinning pain and analgesia and poor animal-to-human translation. Computational pharmacology is currently employed to face these challenges. In this review, we discuss the theory, methods...
Source: Biochemical Pharmacology - February 27, 2024 Category: Drugs & Pharmacology Authors: Ahmed Barakat Gordon Munro Anne-Marie Heegaard Source Type: research
Finding new analgesics: Computational pharmacology faces drug discovery challenges
Biochem Pharmacol. 2024 Feb 25:116091. doi: 10.1016/j.bcp.2024.116091. Online ahead of print.ABSTRACTDespite the worldwide prevalence and huge burden of pain, pain is an undertreated phenomenon. Currently used analgesics have several limitations regarding their efficacy and safety. The discovery of analgesics possessing a novel mechanism of action has faced multiple challenges, including a limited understanding of biological processes underpinning pain and analgesia and poor animal-to-human translation. Computational pharmacology is currently employed to face these challenges. In this review, we discuss the theory, methods...
Source: Biochemical Pharmacology - February 27, 2024 Category: Drugs & Pharmacology Authors: Ahmed Barakat Gordon Munro Anne-Marie Heegaard Source Type: research
Finding new analgesics: Computational pharmacology faces drug discovery challenges
Biochem Pharmacol. 2024 Feb 25:116091. doi: 10.1016/j.bcp.2024.116091. Online ahead of print.ABSTRACTDespite the worldwide prevalence and huge burden of pain, pain is an undertreated phenomenon. Currently used analgesics have several limitations regarding their efficacy and safety. The discovery of analgesics possessing a novel mechanism of action has faced multiple challenges, including a limited understanding of biological processes underpinning pain and analgesia and poor animal-to-human translation. Computational pharmacology is currently employed to face these challenges. In this review, we discuss the theory, methods...
Source: Biochemical Pharmacology - February 27, 2024 Category: Drugs & Pharmacology Authors: Ahmed Barakat Gordon Munro Anne-Marie Heegaard Source Type: research
The 8-hydroxyquinoline derivative, clioquinol, is an alpha-1 adrenoceptor antagonist
Biochem Pharmacol. 2024 Feb 24:116092. doi: 10.1016/j.bcp.2024.116092. Online ahead of print.ABSTRACTClioquinol (5-chloro-7-iodo-8-hydroxyquinoline) is an antimicrobial agent whose actions as a zinc or copper ionophore and an iron chelator revived the interest in similar compounds for the treatment of fungal and bacterial infections, neurodegeneration and cancer. Recently, we reported zinc ionophores, including clioquinol, cause vasorelaxation in isolated arteries through mechanisms that involve sensory nerves, endothelium and vascular smooth muscle. Here, we report that clioquinol also uniquely acts as a competitive alpha...
Source: Biochemical Pharmacology - February 26, 2024 Category: Drugs & Pharmacology Authors: Ashenafi H Betrie Alaa Abdul-Ridha Herodion Hartono David K Chalmers Christine E Wright Daniel J Scott James A Angus Scott Ayton Source Type: research
Decatastrophizing research irreproducibility
Biochem Pharmacol. 2024 Feb 24:116090. doi: 10.1016/j.bcp.2024.116090. Online ahead of print.ABSTRACTThe reported inability to replicate research findings from the published literature precipitated extensive efforts to identify and correct perceived deficiencies in the execution and reporting of biomedical research. Despite these efforts, quantification of the magnitude of irreproducible research or the effectiveness of associated remediation initiatives, across diverse biomedical disciplines, has made little progress over the last decade. The idea that science is self-correcting has been further challenged in recent years...
Source: Biochemical Pharmacology - February 26, 2024 Category: Drugs & Pharmacology Authors: Michael F Jarvis Source Type: research
