Hydrogen Sulfide Lowers Hyperhomocysteinemia Dependent on Cystathionine γ Lyase S-Sulfhydration in ApoE-knockout Atherosclerotic Mice.
Authors of this article are:
Fan J, Zheng F, Li S, Cui C, Jiang S, Zhang J, Cai J, Cui Q, Yang J, Tang X, Xu G, Geng B.
A summary of the article is shown below:
BACKGROUND AND PURPOSE: Hydrogen sulfide (H2S) donors can block the cardiovascular injury effects of hyperhomocysteinemia (HHcy). H2S also lowered serum homocysteine (Hcy) in rats with mild HHcy, but the pharmacological mechanism is unknown. The present study investigated the mechanism.EXPERIMENTAL APPROACH: ApoE-knockout mice fed a Paigen diet and L-methionine in drinking water for 16 weeks were used to create the mouse model of atherosclerosis with HHcy mice. H2S donors (NaHS and GYY4137) were administered by intraperitoneal injection. Next, the H2S product (by methylene blue assay and mito-HS [H2S fluorescence probe]), cystathionine γ lyase (CSE) mRNA and protein expression, and CSE sulfhydration and nitrosylation and its activity were assayed.KEY RESULTS: H2S donor treatment significantly lowered atherosclerotic plaque area, macrophage infiltration and serum Hcy level in the mouse model of atherosclerosis with mediating HHcy. mRNA and protein levels of CSE, a key enzyme of Hcy trans-sulfuration catalysis, were downregulated with HHcy, and CSE catalytic activity was inhibited; all were reversed with H2S donor treatment. Next, HHcy induced CSE nitrosylation, whereas H2S sulfhydrated CSE at the same cysteine sites. Nitrosylated CSE decreased and sulfhydrated CSE increased its catalytic and binding activity to L-Hcy. Mutation of C252, C255, C307 and C310 sites of CSE abolished CSE nitrosylation or sulfhydration and thus eliminated its binding to L-Hcy.CONCLUSIONS AND IMPLICATIONS: Sulfhydration or nitrosylation of CSE represents a yin/yang regulation of catalysis or binding to L-Hcy. H2S donor treatment enhanced CSE sulfhydration, then lowered serum L-Hcy level, which contributed in part to the anti-atherosclerosis effect induced by HHcy.This article is protected by copyright. All rights reserved.
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This article is a good source of information and a good way to become familiar with topics such as: Atherosclerosis; Cystathionine γ lyase; Hydrogen sulfide; Hyperhomocyteinemia; Nitrosylation; Sulfhydration.
