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Start Over Descriptor "CMH" Journal biomolecules
2 results on '"CMH"'

1. CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis

Author

Jenya Konikov-Rozenman, Raphael Breuer, Naftali Kaminski, and Shulamit B. Wallach-Dayan

Subjects
CMH, Ku70-SIRT1, FLIP, apoptosis, fibroblasts, IPF-resolution, Microbiology, QR1-502
Abstract

Regenerative capacity in vital organs is limited by fibrosis propensity. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease linked with aging, is a classic example. In this study, we show that in flow cytometry, immunoblots (IB) and in lung sections, FLIP levels can be regulated, in vivo and in vitro, through SIRT1 activity inhibition by CMH (4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide), a small molecule that, as we determined here by structural biology calculations, docked into its nonhistone substrate Ku70-binding site. Ku70 immunoprecipitations and immunoblots confirmed our theory that Ku70-deacetylation, Ku70/FLIP complex, myofibroblast resistance to apoptosis, cell survival, and lung fibrosis in bleomycin-treated mice, are reduced and regulated by CMH. Thus, small molecules associated with SIRT1-mediated regulation of Ku70 deacetylation, affecting FLIP stabilization in fibrotic-lung myofibroblasts, may be a useful strategy, enabling tissue regeneration.

Published
2020
Full Text
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2. CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis.

Author

Konikov-Rozenman J, Breuer R, Kaminski N, and Wallach-Dayan SB

Subjects
Acetylation drug effects, Animals, Binding Sites, CASP8 and FADD-Like Apoptosis Regulating Protein chemistry, Cell Line, Cell Survival drug effects, Disease Models, Animal, Fibroblasts cytology, Fibroblasts drug effects, Fibroblasts metabolism, Gene Expression Regulation drug effects, Humans, Hydroxamic Acids chemistry, Hydroxamic Acids pharmacology, Idiopathic Pulmonary Fibrosis metabolism, Lung drug effects, Lung metabolism, Male, Mice, Mice, Inbred C57BL, Models, Molecular, Molecular Docking Simulation, Protein Conformation, Protein Stability drug effects, CASP8 and FADD-Like Apoptosis Regulating Protein metabolism, Hydroxamic Acids administration & dosage, Idiopathic Pulmonary Fibrosis drug therapy, Ku Autoantigen metabolism, Lung cytology, Sirtuin 1 chemistry, Sirtuin 1 metabolism
Abstract

Regenerative capacity in vital organs is limited by fibrosis propensity. Idiopathic pulmonary fibrosis (IPF), a progressive lung disease linked with aging, is a classic example. In this study, we show that in flow cytometry, immunoblots (IB) and in lung sections, FLIP levels can be regulated, in vivo and in vitro, through SIRT1 activity inhibition by CMH (4-(4-Chloro-2-methylphenoxy)-N-hydroxybutanamide), a small molecule that, as we determined here by structural biology calculations, docked into its nonhistone substrate Ku70-binding site. Ku70 immunoprecipitations and immunoblots confirmed our theory that Ku70-deacetylation, Ku70/FLIP complex, myofibroblast resistance to apoptosis, cell survival, and lung fibrosis in bleomycin-treated mice, are reduced and regulated by CMH. Thus, small molecules associated with SIRT1-mediated regulation of Ku70 deacetylation, affecting FLIP stabilization in fibrotic-lung myofibroblasts, may be a useful strategy, enabling tissue regeneration.

Published
2020
Full Text
View/download PDF

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