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Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate.

Authors: Liu, Ning  Wu, Jichao  Zhang, Linxue  Gao, Zhaopeng  Sun, Yu  Yu, Miao  Zhao, Yajun  Dong, Shiyun  Lu, Fanghao  Zhang, Weihua 
Citation: Liu N, etal., J Cell Mol Med. 2017 Jun 13. doi: 10.1111/jcmm.13223.
Pubmed: (View Article at PubMed) PMID:28608965
DOI: Full-text: DOI:10.1111/jcmm.13223

Endothelial cell dysfunction is one of the main reasons for type II diabetes vascular complications. Hydrogen sulphide (H2 S) has antioxidative effect, but its regulation on mitochondrial dynamics and mitophagy in aortic endothelial cells under hyperglycaemia and hyperlipidaemia is unclear. Rat aortic endothelial cells (RAECs) were treated with 40 mM glucose and 200 µM palmitate to imitate endothelium under hyperglycaemia and hyperlipidaemia, and 100 µM NaHS was used as an exogenous H2 S donor. Firstly, we demonstrated that high glucose and palmitate decreased H2 S production and CSE expression in RAECs. Then, the antioxidative effect of H2 S was proved in RAECs under high glucose and palmitate to reduce mitochondrial ROS level. We also showed that exogenous H2 S inhibited mitochondrial apoptosis in RAECs under high glucose and palmitate. Using Mito Tracker and transmission electron microscopy assay, we revealed that exogenous H2 S decreased mitochondrial fragments and significantly reduced the expression of p-Drp-1/Drp-1 and Fis1 compared to high-glucose and high-palmitate group, whereas it increased mitophagy by transmission electron microscopy assay. We demonstrated that exogenous H2 S facilitated Parkin recruited by PINK1 by immunoprecipitation and immunostaining assays and then ubiquitylated mitofusin 2 (Mfn2), which illuminated the mechanism of exogenous H2 S on mitophagy. Parkin siRNA suppressed the expression of Mfn2, Nix and LC3B, which revealed that it eliminated mitophagy. In summary, exogenous H2 S could protect RAECs against apoptosis under high glucose and palmitate by suppressing oxidative stress, decreasing mitochondrial fragments and promoting mitophagy. Based on these results, we proposed a new mechanism of H2 S on protecting endothelium, which might provide a new strategy for type II diabetes vascular complication.

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CRRD Object Information
CRRD ID: 13432560
Created: 2017-09-29
Species: All species
Last Modified: 2017-09-29
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.