Cannabidiol induces ERK activation and ROS production to promote autophagy and ferroptosis in glioblastoma cells
Chem Biol Interact. 2024 Apr 5:110995. doi: 10.1016/j.cbi.2024.110995. Online ahead of print.ABSTRACTSmall molecule-driven ERK activation is known to induce autophagy and ferroptosis in cancer cells. Herein the effect of cannabidiol (CBD), a phytochemical derived from Cannabis sativa, on ERK-driven autophagy and ferroptosis has been demonstrated in glioblastoma (GBM) cells (U87 and U373 cells). CBD imparted significant cytotoxicity in GBM cells, induced activation of ERK (not JNK and p38), and increased intracellular reactive oxygen species (ROS) levels. It increased the autophagy-related proteins such as LC3 II, Atg7, and...
Source: Chemico-Biological Interactions - April 7, 2024 Category: Molecular Biology Authors: Na Young Kim Siddegowda Gopalapura Shivanne Gowda Seok-Geun Lee Gautam Sethi Kwang Seok Ahn Source Type: research
Inhibitory effects of black phosphorus nanosheets on tumor cell proliferation through downregulation of ADIPOQ and downstream signaling pathways
Chem Biol Interact. 2024 Apr 4:110994. doi: 10.1016/j.cbi.2024.110994. Online ahead of print.ABSTRACTExposure to environmental pollutants, including nanomaterials, has a significant impact on tumor progression. The increased demand for black phosphorus nanosheets (BPNSs), driven by their exceptional properties, raises concerns about potential environmental contamination. Assessing their toxicity on tumor growth is essential. Herein, we employed a range of biological techniques, including cytotoxicity measurement, bioinformatics tools, proteomics, target gene overexpression, Western blot analysis, and apoptosis detection, t...
Source: Chemico-Biological Interactions - April 6, 2024 Category: Molecular Biology Authors: Daxu Liu Qing Zhao Zhaoxu Tu Siyu Zhang Shuo Deng Zhiqiang Xiong Jin Zeng Fengchang Wu Xuejiao Zhang Baoshan Xing Source Type: research
A tipping point in dihydroxyacetone exposure: mitochondrial stress and metabolic reprogramming alter survival in rat cardiomyocytes H9c2 cells
Chem Biol Interact. 2024 Apr 4;394:110991. doi: 10.1016/j.cbi.2024.110991. Online ahead of print.ABSTRACTExogenous exposures to the triose sugar dihydroxyacetone (DHA) occur from sunless tanning products and electronic cigarette aerosol. Once inhaled or absorbed, DHA enters cells, is converted to dihydroxyacetone phosphate (DHAP), and incorporated into several metabolic pathways. Cytotoxic effects of DHA vary across the cell types depending on the metabolic needs of the cells, and differences in the generation of reactive oxygen species (ROS), cell cycle arrest, and mitochondrial dysfunction have been reported. We have sho...
Source: Chemico-Biological Interactions - April 6, 2024 Category: Molecular Biology Authors: Arlet Hernandez Luxene Belfleur Marie Migaud Natalie R Gassman Source Type: research
Inhibitory effects of black phosphorus nanosheets on tumor cell proliferation through downregulation of ADIPOQ and downstream signaling pathways
Chem Biol Interact. 2024 Apr 4:110994. doi: 10.1016/j.cbi.2024.110994. Online ahead of print.ABSTRACTExposure to environmental pollutants, including nanomaterials, has a significant impact on tumor progression. The increased demand for black phosphorus nanosheets (BPNSs), driven by their exceptional properties, raises concerns about potential environmental contamination. Assessing their toxicity on tumor growth is essential. Herein, we employed a range of biological techniques, including cytotoxicity measurement, bioinformatics tools, proteomics, target gene overexpression, Western blot analysis, and apoptosis detection, t...
Source: Chemico-Biological Interactions - April 6, 2024 Category: Molecular Biology Authors: Daxu Liu Qing Zhao Zhaoxu Tu Siyu Zhang Shuo Deng Zhiqiang Xiong Jin Zeng Fengchang Wu Xuejiao Zhang Baoshan Xing Source Type: research
A tipping point in dihydroxyacetone exposure: Mitochondrial stress and metabolic reprogramming alter survival in rat cardiomyocytes H9c2 cells
Chem Biol Interact. 2024 Apr 4:110991. doi: 10.1016/j.cbi.2024.110991. Online ahead of print.ABSTRACTExogenous exposures to the triose sugar dihydroxyacetone (DHA) occur from sunless tanning products and electronic cigarette aerosol. Once inhaled or absorbed, DHA enters cells, is converted to dihydroxyacetone phosphate (DHAP), and incorporated into several metabolic pathways. Cytotoxic effects of DHA vary across the cell types depending on the metabolic needs of the cells, and differences in the generation of reactive oxygen species (ROS), cell cycle arrest, and mitochondrial dysfunction have been reported. We have shown t...
Source: Chemico-Biological Interactions - April 6, 2024 Category: Molecular Biology Authors: Arlet Hernandez Luxene Belfleur Marie Migaud Natalie R Gassman Source Type: research
Autophagic-lysosomal damage induced by swainsonine is protected by trehalose through activation of TFEB-regulated pathway in renal tubular epithelial cells
In this study, we investigate the mechanism of protective effects of trehalose using renal tubular epithelial cells. The results showed that SW induced an increase in the expression level of microtubule-associated protein light chain 3-II and p62 proteins and a decrease in the expression level of ATPase H+ transporting V1 Subunit A, Cathepsin B, Cathepsin D, lysosome-associated membrane protein 2 and TFEB proteins in renal tubular epithelial cells in a time and dose-dependent manner suggesting TFEB-regulated lysosomal pathway is adversely affected by SW. Conversely, treatment with trehalose, a known activator of TFEB promo...
Source: Chemico-Biological Interactions - April 5, 2024 Category: Molecular Biology Authors: Shuhang Zhang Hai Yin Yiqingqing Zhang Yanli Zhu Xueyao Zhu Wenting Zhu Lihui Tang Yiling Liu Kexin Wu Baoyu Zhao Yanan Tian Hao Lu Source Type: research
Substitution of both histidines in the active site of yeast alcohol dehydrogenase 1 exposes underlying pH dependencies
Chem Biol Interact. 2024 Apr 3:110992. doi: 10.1016/j.cbi.2024.110992. Online ahead of print.ABSTRACTHistidine residues 44 and 48 in yeast alcohol dehydrogenase (ADH) bind to the coenzymes NAD(H) and contribute to catalysis. The individual H44R and H48Q substitutions alter the kinetics and pH dependencies, and now the roles of other ionizable groups in the enzyme were studied in the doubly substituted H44R/H48Q ADH. The substitutions make the enzyme more resistant to inactivation by diethyl pyrocarbonate, modestly improve affinity for coenzymes, and substantially decrease catalytic efficiencies for ethanol oxidation and ac...
Source: Chemico-Biological Interactions - April 5, 2024 Category: Molecular Biology Authors: Tobias Jacobi Darla Ann Kratzer Bryce V Plapp Source Type: research
Autophagic-lysosomal damage induced by swainsonine is protected by trehalose through activation of TFEB-regulated pathway in renal tubular epithelial cells
In this study, we investigate the mechanism of protective effects of trehalose using renal tubular epithelial cells. The results showed that SW induced an increase in the expression level of microtubule-associated protein light chain 3-II and p62 proteins and a decrease in the expression level of ATPase H+ transporting V1 Subunit A, Cathepsin B, Cathepsin D, lysosome-associated membrane protein 2 and TFEB proteins in renal tubular epithelial cells in a time and dose-dependent manner suggesting TFEB-regulated lysosomal pathway is adversely affected by SW. Conversely, treatment with trehalose, a known activator of TFEB promo...
Source: Chemico-Biological Interactions - April 5, 2024 Category: Molecular Biology Authors: Shuhang Zhang Hai Yin Yiqingqing Zhang Yanli Zhu Xueyao Zhu Wenting Zhu Lihui Tang Yiling Liu Kexin Wu Baoyu Zhao Yanan Tian Hao Lu Source Type: research
Substitution of both histidines in the active site of yeast alcohol dehydrogenase 1 exposes underlying pH dependencies
Chem Biol Interact. 2024 Apr 3:110992. doi: 10.1016/j.cbi.2024.110992. Online ahead of print.ABSTRACTHistidine residues 44 and 48 in yeast alcohol dehydrogenase (ADH) bind to the coenzymes NAD(H) and contribute to catalysis. The individual H44R and H48Q substitutions alter the kinetics and pH dependencies, and now the roles of other ionizable groups in the enzyme were studied in the doubly substituted H44R/H48Q ADH. The substitutions make the enzyme more resistant to inactivation by diethyl pyrocarbonate, modestly improve affinity for coenzymes, and substantially decrease catalytic efficiencies for ethanol oxidation and ac...
Source: Chemico-Biological Interactions - April 5, 2024 Category: Molecular Biology Authors: Tobias Jacobi Darla Ann Kratzer Bryce V Plapp Source Type: research
Decoding epilepsy treatment: A comparative evaluation contrasting cannabidiol pharmacokinetics in adult and paediatric populations
Chem Biol Interact. 2024 Apr 3;394:110988. doi: 10.1016/j.cbi.2024.110988. Online ahead of print.ABSTRACTEpilepsy is a neurological disorder characterized by overstimulation of neurotransmitters and uncontrolled seizures. Current medications for epilepsy result in adverse effects or insufficient seizure control, highlighting the necessity to develop alternative therapies. Cannabidiol (CBD), derived from cannabis plants, has been popularly explored as an alternative. CBD is shown to have anti-convulsivatng and muscle-relaxing properties, which have been used in patients with epilepsy with promising results. Current research...
Source: Chemico-Biological Interactions - April 4, 2024 Category: Molecular Biology Authors: Mohamed Osman Jamileh Khalil Mostafa El-Bahri Jamal Swalah Mcdahrou Reem Fahda Reymin Mustafa Arthur Ooi Marwa Attayee Rachelle Catanzariti Lisa Pont Kylie Williams Stewart Yeung Kamal Dua Gabriele De Rubis Raimar Loebenberg Source Type: research
Carbon-chain length determines the binding affinity and inhibitory strength of per- and polyfluoroalkyl substances on human and rat steroid 5 α-reductase 1 activity
This study investigated the inhibitory strength and binding interactions of 18 PFAS on human and rat SRD5A1 activity using enzyme assays, molecular docking, and structure-activity relationship analysis. Results revealed that C9-C14 PFAS carboxylic acid at 100 μM significantly inhibited human SRD5A1, with IC50 values ranged from 10.99 μM (C11) to 105.01 μM (C14), and only one PFAS sulfonic acid (C8S) significantly inhibited human SRD5A1 activity, with IC50 value of 8.15 μM. For rat SRD5A1, C9-C14 PFAS inhibited rat SRD5A1, showing the similar trend, depending on carbon number of the carbon chain. PFAS inhibit human and ...
Source: Chemico-Biological Interactions - April 4, 2024 Category: Molecular Biology Authors: Rong Cui Lei Ye Xinyi Qiao Shaowei Wang Ke Zheng Jin Yang Ren-Shan Ge Han Lin Yiyan Wang Source Type: research
The thiol methyltransferase activity of TMT1A (METTL7A) is conserved across species
Chem Biol Interact. 2024 Apr 2:110989. doi: 10.1016/j.cbi.2024.110989. Online ahead of print.ABSTRACTAlthough few resistance mechanisms for histone deacetylase inhibitors (HDACis) have been described, we recently demonstrated that TMT1A (formerly METTL7A) and TMT1B (formerly METTL7B) can mediate resistance to HDACis with a thiol as the zinc-binding group by methylating and inactivating the drug. TMT1A and TMT1B are poorly characterized, and their normal physiological role has yet to be determined. As animal model systems are often used to determine the physiological function of proteins, we investigated whether the ability...
Source: Chemico-Biological Interactions - April 4, 2024 Category: Molecular Biology Authors: Jos é M González Dalmasy Christina M Fitzsimmons William J E Frye Andrew J Perciaccante Connor P Jewell Lisa M Jenkins Pedro J Batista Robert W Robey Michael M Gottesman Source Type: research
The risk associated with organophosphorus nerve agents: from their discovery to their unavoidable threat, current medical countermeasures and perspectives
Chem Biol Interact. 2024 Apr 2:110973. doi: 10.1016/j.cbi.2024.110973. Online ahead of print.ABSTRACTThe first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after the first use of chemical weapons (chlorine, phosgene) on the battlefield during World War I. Despite the Chemical Weapons Convention banning these substances, they have still been employed in wars, terrorist attacks or political assassinations. Characterised by their high lethality, they target the nervous system by inhibiting the acetylcholinesterase (AChE) enzyme, preventing neurotransmission, which, if no...
Source: Chemico-Biological Interactions - April 4, 2024 Category: Molecular Biology Authors: Camille Voros Jos é Dias Christopher M Timperley Florian Nachon Richard C D Brown Rachid Baati Source Type: research
A 50-gene biomarker identifies estrogen receptor-modulating chemicals in a microarray compendium
We describe here the construction and characterization of a 50-gene expression biomarker designed to identify estrogen receptor (ER) active chemicals in HTTr datasets. Using microarray comparisons, the genes in the biomarker were identified as those that exhibited consistent directional changes when ER was activated (4 ER agonists; 4 ESR1 gene constitutively active mutants) and opposite directional changes when ER was suppressed (4 antagonist treatments; 4 ESR1 knockdown experiments). The biomarker was evaluated as a predictive tool using the Running Fisher algorithm by comparison to annotated gene expression microarray da...
Source: Chemico-Biological Interactions - April 3, 2024 Category: Molecular Biology Authors: J Christopher Corton Geronimo Matteo Brian Chorley Jie Liu Beena Vallanat Logan Everett Ella Atlas Matthew J Meier Andrew Williams Carole Lyn Yauk Source Type: research
A 50-gene biomarker identifies estrogen receptor-modulating chemicals in a microarray compendium
We describe here the construction and characterization of a 50-gene expression biomarker designed to identify estrogen receptor (ER) active chemicals in HTTr datasets. Using microarray comparisons, the genes in the biomarker were identified as those that exhibited consistent directional changes when ER was activated (4 ER agonists; 4 ESR1 gene constitutively active mutants) and opposite directional changes when ER was suppressed (4 antagonist treatments; 4 ESR1 knockdown experiments). The biomarker was evaluated as a predictive tool using the Running Fisher algorithm by comparison to annotated gene expression microarray da...
Source: Chemico-Biological Interactions - April 3, 2024 Category: Molecular Biology Authors: J Christopher Corton Geronimo Matteo Brian Chorley Jie Liu Beena Vallanat Logan Everett Ella Atlas Matthew J Meier Andrew Williams Carole Lyn Yauk Source Type: research
