Tyagi Neetu, Moshal Karni S, Sen Utpal, Vacek Thomas P, Kumar Munish, Hughes William M, Kundu Soumi, Tyagi Suresh C
Department of Physiology and Biophysics, School of Medicine, University of Louisville, Louisville, Kentucky 40202, USA.
Antioxid Redox Signal. 2009 Jan;11(1):25-33. doi: 10.1089/ars.2008.2073.
Homocysteine (Hcy) causes cerebrovascular dysfunction by inducing oxidative stress. However, to date, there are no strategies to prevent Hcy-induced oxidative damage. Hcy is an H2S precursor formed from methionine (Met) metabolism. We aimed to investigate whether H2S ameliorated Met-induced oxidative stress in mouse brain endothelial cells (bEnd3). The bEnd3 cells were exposed to Met treatment in the presence or absence of NaHS (donor of H2S). Met-induced cell toxicity increased the levels of free radicals in a concentration-dependent manner. Met increased NADPH-oxidase-4 (NOX-4) expression and mitigated thioredxion-1(Trx-1) expression. Pretreatment of bEnd3 with NaHS (0.05 mM) attenuated the production of free radicals in the presence of Met and protected the cells from oxidative damage. Furthermore, NaHS enhanced inhibitory effects of apocynin, N-acetyl-l-cysteine (NAC), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), Nomega-nitro-l-arginine methyl ester (L-NAME) on ROS production and redox enzymes levels induced by Met. In conclusion, the administration of H2S protected the cells from oxidative stress induced by hyperhomocysteinemia (HHcy), which suggested that NaHS/H2S may have therapeutic potential against Met-induced oxidative stress.
同型半胱氨酸（Hcy）通过诱导氧化应激导致脑血管功能障碍。然而，迄今为止，尚无预防Hcy诱导的氧化损伤的策略。Hcy是由甲硫氨酸（Met）代谢形成的H2S前体。我们旨在研究H2S是否能改善Met诱导的小鼠脑内皮细胞（bEnd3）中的氧化应激。在存在或不存在NaHS（H2S供体）的情况下，将bEnd3细胞暴露于Met处理。Met诱导的细胞毒性以浓度依赖的方式增加自由基水平。Met增加了NADPH氧化酶4（NOX-4）的表达并减轻了硫氧还蛋白-1（Trx-1）的表达。用NaHS（0.05 mM）预处理bEnd3可在存在Met的情况下减弱自由基的产生，并保护细胞免受氧化损伤。此外，NaHS增强了载脂蛋白、N-乙酰-L-半胱氨酸（NAC）、还原型谷胱甘肽（GSH）、过氧化氢酶（CAT）、超氧化物歧化酶（SOD）、Nω-硝基-L-精氨酸甲酯（L-NAME）对Met诱导的ROS产生和氧化还原酶水平的抑制作用。总之，给予H2S可保护细胞免受高同型半胱氨酸血症（HHcy）诱导的氧化应激，这表明NaHS/H2S可能具有对抗Met诱导的氧化应激的治疗潜力。
