Published online before print February 28, 2002, doi: 10.1161/01.ATV.0000013785.03265.5C
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© 2002 American Heart Association, Inc.
Vascular Biology |
Vitamin C Protects Against Hypochlorous Acid–Induced Glutathione Depletion and DNA Base and Protein Damage in Human Vascular Smooth Muscle Cells
From the Centre for Cardiovascular Biology and Medicine (A.J., E.R., C.D., G.E.M., R.C.M.S.), Guy’s, King’s and St. Thomas’ School of Biomedical Sciences, King’s College, University of London, London, UK, and the Department of Biochemistry (A.J., B.H.), National University of Singapore, Republic of Singapore.
Correspondence to Dr R.C.M. Siow, Centre for Cardiovascular Biology and Medicine GKT School of Biomedical Sciences, King’s College, University of London, Guy’s Hospital Campus, London SE1 1UL, UK. E-mail richard.siow{at}kcl.ac.uk
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 µmol/L vitamin C (24 hours) and then exposed to HOCl (0 to 500 µmol/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.
Key Words: vascular smooth muscle cells • vitamin C • hypochlorous acid • DNA • atherosclerosis
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