Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong.
PLoS One. 2018 Mar 8;13(3):e0194176. doi: 10.1371/journal.pone.0194176. eCollection 2018.
S-sulfhydration is a signalling pathway of hydrogen sulfide (H2S), which is suggested as an anti-atherogenic molecule that may protect against atherosclerosis. The identification of S-sulfhydrated proteins by proteomic approach could be a major step towards understanding the mechanisms of H2S in response to atherosclerosis. The present study studied targeted S-sulfhydrated proteins using the modified biotin switch method followed by matrix-assisted laser desorption/ionisation time of flight tandem mass spectrometry identification. The results showed that H2S can protect against atherosclerosis by reducing body weight gain and alleviating aortic plaque formation. In addition, H2S treatment can increase aortic protein S-sulfhydration. Seventy targeted S-sulfhydrated aortic proteins were identified, mainly involved in metabolism, stimulus response and biological regulation, as determined by gene ontology database analysis. H2S also induced S-sulfhydration of glutathione peroxidase 1 and further reduced lipid peroxidation and increased antioxidant defence in the aorta by prompting glutathione synthesis. Our data suggest that H2S is a cardiovascular-protective molecule that S-sulfhydrates a subset of proteins that are mainly responsible for lipid metabolism and exerts its cytoprotective effects to clear free radicals and inhibit oxidative stress through cysteine S-sulfhydration.
S-巯基化是硫化氢 (H2S) 的信号通路，H2S 被认为是一种抗动脉粥样硬化分子，可能对动脉粥样硬化有保护作用。通过蛋白质组学方法鉴定 S-巯基化蛋白质可能是理解 H2S 对动脉粥样硬化反应机制的重要步骤。本研究采用改良的生物素交换法，结合基质辅助激光解吸/电离飞行时间串联质谱鉴定，研究了靶向 S-巯基化蛋白质。结果表明，H2S 通过减轻体重增加和缓解主动脉斑块形成来预防动脉粥样硬化。此外，H2S 处理可增加主动脉蛋白 S-巯基化。通过基因本体数据库分析，确定了 70 种靶向 S-巯基化主动脉蛋白，主要涉及代谢、刺激反应和生物调节。H2S 还通过诱导谷胱甘肽过氧化物酶 1 的 S-巯基化，进一步减少脂质过氧化，并通过促进谷胱甘肽合成增加主动脉的抗氧化防御能力。我们的数据表明，H2S 是一种心血管保护分子，它使一组主要负责脂质代谢的蛋白质发生 S-巯基化，并通过半胱氨酸 S-巯基化清除自由基和抑制氧化应激来发挥其细胞保护作用。
