期刊
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
卷 116, 期 -, 页码 29-40出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2018.01.011
关键词
Hydrogen sulfide; Mitochondria; Heart; AMPK
资金
- American Heart Association [15POST25610016, 16GRNT31190016]
- National Institutes of Health (NIH) [1R01DK115213-01, 5R01HL098481-05, 1R01HL092141, 1R01HL093579, 1U24HL094373, 1P20HL113452]
- Carlyle Fraser Heart Center of Emory University Hospital Midtown
- Canadian Institutes of Health Research [MOP 119565]
Background: Hydrogen sulfide (H2S) is an important regulator of mitochondrial bioenergetics, but its role in regulating mitochondrial biogenesis is not well understood. Using both genetic and pharmacological approaches, we sought to determine if H2S levels directly influenced cardiac mitochondrial content. Results: Mice deficient in the H2S-producing enzyme, cystathionine gamma-lyase (CSE KO) displayed diminished cardiac mitochondrial content when compared to wild-type hearts. In contrast, mice overexpressing CSE (CSE Tg) and mice supplemented with the orally active H2S-releasing prodrug, SG-1002, displayed enhanced cardiac mitochondrial content. Additional analysis revealed that cardiac H2S levels influenced the nuclear localization and transcriptional activity of peroxisome proliferator-activated receptor gamma coactivator la (PGC1 alpha) with higher levels having a positive influence and lower levels having a negative influence. Studies aimed at evaluating the underlying mechanisms found that H2S required AMP-activated protein kinase (AMPK) to induce PGC1 alpha signaling and mitochondrial biogenesis. Finally, we found that restoring H2S levels with SG-1002 in the setting of heart failure increased cardiac mitochondrial content, improved mitochondrial respiration, improved ATP production efficiency, and improved cardiac function. Conclusions: Together, these results suggest that hydrogen sulfide is an important regulator of cardiac mitochondrial content and establishes that exogenous hydrogen sulfide can induce mitochondrial biogenesis via an AMPK-PGC1 alpha signaling cascade.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据