Key result
Nitric oxide protects endothelial cells against apoptosis by inhibiting SOD1 monomerization to reduce oxidative stress.
Why the study?
Endothelial cell apoptosis contributes to many cardiovascular diseases, and while nitric oxide regulates cell survival and apoptosis, the underlying mechanism remains unclear.
This study identifies a novel mechanism by which nitric oxide prevents endothelial cell apoptosis via inhibition of cysteine-dependent SOD1 monomerization.
Hypothesis-generating for NO-SOD1 endothelial protection; clinical translation requires further validation.
Endothelial cell apoptosis is an important pathophysiology in many cardiovascular diseases. The gasotransmitter nitric oxide (NO) is known to regulate cell survival and apoptosis. However, the mechanism underlying the effect of NO remains unclear. In this research, by targeting cytosolic copper/zinc superoxide dismutase (SOD1) monomerization, we aimed to explore how NO inhibited endothelial cell apoptosis. We showed that treatment with the NO synthase (NOS) inhibitor nomega-nitro-l-arginine methyl ester hydrochloride (L-NAME) significantly decreased the endogenous NO content of endothelial cells, facilitated the formation of SOD1 monomers, inhibited dismutase activity, and promoted reactive oxygen species (ROS) accumulation in human umbilical vein endothelial cells (HUVECs); by contrast, supplementation with the NO donor sodium nitroprusside (SNP) upregulated NO content, prevented the formation of SOD1 monomers, enhanced dismutase activity, and reduced ROS accumulation in L-NAME-treated HUVECs. Mechanistically, tris(2-carboxyethyl) phosphine hydrochloride (TCEP), a specific reducer of cysteine thiol, increased SOD1 monomer formation, thus preventing the NO-induced increase in dismutase activity and the decrease in ROS. Furthermore, SNP inhibited HUVEC apoptosis caused by the decrease in endogenous NO, whereas TCEP abolished this protective effect of SNP. In summary, our data reveal that NO protects endothelial cells against apoptosis by inhibiting cysteine-dependent SOD1 monomerization to enhance SOD1 activity and inhibit oxidative stress.
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Peng et al. (2022) studied Endothelial cell apoptosis. Nitric oxide (NO) / Sodium nitroprusside (SNP) vs. L-NAME / TCEP was evaluated on Endothelial cell apoptosis and SOD1 monomerization. Nitric oxide protects endothelial cells against apoptosis by inhibiting cysteine-dependent SOD1 monomerization to enhance SOD1 activity and inhibit oxidative stress.
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