Endogenous H2 S resists mitochondria-mediated apoptosis in the adrenal glands via ATP5A1 S-sulfhydration in male mice

Molecular and Cellular Endocrinology
Changnan WangXin Ni

Abstract

In a previous study, we showed that endogenous hydrogen sulfide (H2S) plays a key role in the maintenance of intact adrenal cortex function via the protection of mitochondrial function during endoxemia. We further investigated whether mitochondria-mediated apoptosis is involved in H2S protection of adrenal function. LPS treatment resulted in mitochondria-mediated apoptosis in the adrenal glands of male mice, and these effects were prevented by the H2S donor GYY4137. In the model of Y1 cells, the LPS-induced mitochondria-mediated apoptosis and blunt response to ACTH were rescued by GYY4137. The H2S-generating enzyme cystathionine-β-synthase (CBS) knockout heterozygous (CBS+/-) mice showed mitochondria-mediated apoptosis in the adrenal gland and adrenal insufficiency. GYY4137 treatment restored adrenal function and eliminated mitochondria-mediated apoptosis. Maleimide assay combined with mass spectrometry analysis showed that a number of proteins in mitochondria were S-sulfhydrated in the adrenal gland. ATP5A1 was further confirmed as S-sulfhydrated using a modified biotin switch assay. The level of S-sulfhydrated ATP5A1 was decreased in the adrenal gland of endotoxemic and CBS+/- mice, which was restored by GYY4137. ATP5A1 was i...Continue Reading

Citations

Jun 18, 2019·Critical Care Medicine·Chu-Fan XuLai Jiang
Oct 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Brennah MurphyPriyabrata Mukherjee
Feb 7, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ji GengZheng-Hong Qin
Aug 3, 2021·Frontiers in Endocrinology·Hao-Jie ChenDong-Dong Wu

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