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Protective effect of hydrogen sulfide on endothelial cells through Sirt1-FoxO1-mediated autophagy.


ABSTRACT:

Background

As a new member of the vasculoprotective gasotransmitter family, hydrogen sulfide (H2S) functions similar to nitric oxide (NO) and carbon monoxide (CO). Endothelial cell (EC) death and autophagy enable cells to cope with the progression of cardiovascular diseases. However, the impacts and underlying mechanisms of H2S in the autophagic process in ECs are not completely understood. Here, we investigated the effects of H2S on autophagy in human vascular ECs.

Methods

Human umbilical vein endothelial cells (HUVECs) were exposed to different concentrations (0, 50, 100, 200, 500 and 1,000 µmol/L) GYY4137 (H2S donor) for indicated times (0, 0.5, 1, 2, 4 and 8 h), with or without pre-treatment with the autophagy inhibitor 3-methyladenine (3-MA) or bafilomycin A1. HUVECs were transfected with sirtuin 1 (Sirt1) overexpression plasmids (PIRES-Sirt1), Sirt1-siRNAs or forkhead box O1 (FoxO1)-siRNA using Lipofectamine 2000. Cell autophagy was evaluated via Western blotting and fluorescence microscopy. Co-immunoprecipitation assay was used to measure acetylation level of FoxO1. The distribution of FoxO1 in the cytoplasm and nucleus was observed using Western blotting and immunofluorescence. Western blotting, flow cytometric analysis, and cell count kit-8 assay were conducted to evaluate the effect of H2S on the oxidized low-density lipoprotein (Ox-LDL) induced apoptosis of HUVECs.

Results

Using both gain- and loss-of-function experiments, we showed that Sirt1-dependent activation of FoxO1, including its nuclear translocation and deacetylation, was critical for mediating H2S-induced autophagy in ECs. Furthermore, H2S-induced autophagy protected ECs from Ox-LDL-induced apoptosis by activating Sirt1.

Conclusions

These results suggest that Sirt1-mediated autophagy in ECs is a novel mechanism by which H2S exerts vascular-protective actions.

SUBMITTER: Zhu L 

PROVIDER: S-EPMC7791216 | biostudies-literature |

REPOSITORIES: biostudies-literature

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