Jenner Andrew M, Ruiz J Emilio, Dunster Christina, Halliwell Barry, Mann Giovanni E, Siow Richard C M
Centre for Cardiovascular Biology and Medicine, Guy's, King's and St. Thomas' School of Biomedical Sciences, King's College, University of London, London, UK.
Arterioscler Thromb Vasc Biol. 2002 Apr 1;22(4):574-80. doi: 10.1161/01.atv.0000013785.03265.5c.
Hypochlorous acid (HOCl), generated by myeloperoxidase released from activated macrophages, is thought to contribute to vascular dysfunction and oxidation of low density lipoproteins (LDLs) in atherogenesis. We have previously shown that HOCl exposure can cause chlorination and oxidation of isolated DNA and that vitamin C protects human arterial smooth muscle cells against oxidized LDL-mediated damage. We report in the present study that vitamin C attenuates HOCl-induced DNA base and protein damage and depletion of intracellular glutathione (GSH) and ATP in human arterial smooth muscle cells. Cells were pretreated in the absence or presence of 100 micromol/L vitamin C (24 hours) and then exposed to HOCl (0 to 500 micromol/L, 0 to 60 minutes) in the absence of vitamin C. Intracellular GSH and ATP levels were depleted by HOCl treatment, and gas chromatography-mass spectroscopy revealed a concentration- and time-dependent increase in DNA base oxidation and protein damage (measured as 3-chlorotyrosine). Pretreatment of smooth muscle cells with vitamin C significantly reduced the extent of HOCl-induced DNA and protein damage and attenuated decreases in intracellular ATP and GSH. Our findings suggest that physiological levels of vitamin C provide an important antioxidant defense against HOCl-mediated injury in atherosclerosis.
由活化巨噬细胞释放的髓过氧化物酶产生的次氯酸（HOCl）被认为在动脉粥样硬化形成过程中会导致血管功能障碍和低密度脂蛋白（LDL）氧化。我们之前已经表明，HOCl暴露会导致分离的DNA发生氯化和氧化，并且维生素C可保护人动脉平滑肌细胞免受氧化型LDL介导的损伤。我们在本研究中报告，维生素C可减轻HOCl诱导的人动脉平滑肌细胞中的DNA碱基和蛋白质损伤以及细胞内谷胱甘肽（GSH）和ATP的消耗。细胞在不存在或存在100微摩尔/升维生素C的情况下预处理（24小时），然后在不存在维生素C的情况下暴露于HOCl（0至500微摩尔/升，0至60分钟）。HOCl处理会使细胞内GSH和ATP水平降低，气相色谱 - 质谱分析显示DNA碱基氧化和蛋白质损伤（以3 - 氯酪氨酸测量）呈浓度和时间依赖性增加。用维生素C预处理平滑肌细胞可显著降低HOCl诱导的DNA和蛋白质损伤程度，并减轻细胞内ATP和GSH的降低。我们的研究结果表明，生理水平的维生素C可提供重要的抗氧化防御，以抵御动脉粥样硬化中HOCl介导的损伤。
