TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide


Endothelial dysfunction is implicated in the development and aggravation of cardiovascular complications. Among the endothelium-released vasoactive factors, hydrogen sulfide (H2S) has been investigated for its beneficial effects on the vasculature through anti-inflammatory and redox-modulating regulatory mechanisms. Reduced H2S bioavailability is reported in chronic diseases such as cardiovascular disease, diabetes, atherosclerosis and preeclampsia, suggesting the value of investigating mechanisms, by which H2S acts as a vasoprotective gasotransmitter. We explored whether the protective effects of H2S were linked to the mitochondrial health of endothelial cells and the mechanisms by which H2S rescues apoptosis. Here, we demonstrate that endothelial dysfunction induced by TNF-α increased endothelial oxidative stress and induced apoptosis via mitochondrial cytochrome c release and caspase activation over 24 h. TNF-α also affected mitochondrial morphology and altered the mitochondrial network. Post-treatment with the slow-releasing H2S donor, GYY4137, alleviated oxidising redox state, decreased pro-caspase 3 activity, and prevented endothelial apoptosis caused by TNF-α alone. In addition, exogenous GYY4137 enhanced S-sulfhydration of pro-caspase 3 and improved mitochondrial health in TNF-α exposed cells. These data provide new insights into molecular mechanisms for cytoprotective effects of H2S via the mitochondrial-driven pathway.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences > Aston Medical School > Translational Medicine Research Group (TMRG)
College of Health & Life Sciences > Aston Medical School
College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
Additional Information: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (
Uncontrolled Keywords: hydrogen sulfide,inflammation,mitochondrial function,oxidative stress,vascular dysfunction,Food Science,Physiology,Biochemistry,Molecular Biology,Clinical Biochemistry,Cell Biology
Publication ISSN: 2076-3921
Last Modified: 27 May 2024 07:40
Date Deposited: 27 Mar 2023 13:23
Full Text Link:
Related URLs: https://www.mdp ... 6-3921/12/3/734 (Publisher URL)
PURE Output Type: Article
Published Date: 2023-03-16
Published Online Date: 2023-03-16
Accepted Date: 2023-03-13
Authors: Diaz Sanchez, Lorena
Sanchez-Aranguren, Lissette (ORCID Profile 0000-0002-4663-5752)
Wang, Keqing (ORCID Profile 0000-0001-6239-6344)
Spickett, Corinne M. (ORCID Profile 0000-0003-4054-9279)
Griffiths, Helen R.
Dias, Irundika H. K. (ORCID Profile 0000-0002-6620-8221)



Version: Published Version

License: Creative Commons Attribution

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