Intracellular H2S production is an autophagy-dependent adaptive response to DNA damage.
Cell Chem Biol
; 28(12): 1669-1678.e5, 2021 12 16.
Article
em En
| MEDLINE
| ID: mdl-34166610
ABSTRACT
Hydrogen sulfide (H2S) is a gasotransmitter with broad physiological activities, including protecting cells against stress, but little is known about the regulation of cellular H2S homeostasis. We have performed a high-content small-molecule screen and identified genotoxic agents, including cancer chemotherapy drugs, as activators of intracellular H2S levels. DNA damage-induced H2S in vitro and in vivo. Mechanistically, DNA damage elevated autophagy and upregulated H2S-generating enzyme CGL; chemical or genetic disruption of autophagy or CGL impaired H2S induction. Importantly, exogenous H2S partially rescued autophagy-deficient cells from genotoxic stress. Furthermore, stressors that are not primarily genotoxic (growth factor depletion and mitochondrial uncoupler FCCP) increased intracellular H2S in an autophagy-dependent manner. Our findings highlight the role of autophagy in H2S production and suggest that H2S generation may be a common adaptive response to DNA damage and other stressors.
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Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Bibliotecas de Moléculas Pequenas
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Sulfeto de Hidrogênio
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Antineoplásicos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article