The impaired glutathione system and its up-regulation by sulforaphane in vascular smooth muscle cells from spontaneously hypertensive rats.
The glutathione (GSH) system plays an important role in reducing oxidative stress, the increase of which has been linked to the pathogenesis of hypertension. The aims of this study were to investigate: (1) whether the GSH system was impaired in aortic smooth muscle cells (SMCs) from spontaneously hypertensive rats (SHR), and (2) whether this system could be up-regulated by the phase-2 enzyme inducers, sulforaphane and t-butylhydroquinone (t-BHQ). Basal levels of cellular GSH, GSH-reductase and GSH-peroxidase were significantly lower in SMCs from SHR than from normotensive Wistar-Kyoto (WKY) rats. Heme oxygenase-1 (HO-1) was significantly higher in SHR SMCs, which correlated with the higher oxidative stress experienced by these cells. No differences were observed in the basal activity of GSH-S-transferase nor in the ability to synthesize GSH between SMCs from these two strains. Sulforaphane (0.05-1 micromol/l) and t-BHQ (10-100 micromol/l) induced significant and concentration-dependent increases in cellular GSH levels, HO-1 protein content and activities of GSH-reductase and GSH-peroxidase in SMCs from both rat strains. Upregulation of phase 2 enzymes correlated with a decrease in oxidative stress experienced by the SMCs, particularly with SHR. We conclude that SHR SMCs experience greater oxidative stress than WKY SMCs and that malfunction of the GSH system contributes to the enhanced oxidative stress in SHR SMCs.
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Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, SK, Canada S7N 5E5.
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D000818:Animals; D002478:Cells, Cultured; D005978:Glutathione / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006873:Hydroquinones / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism*; D017879:Isothiocyanates; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011921:Rats, Inbred WKY; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*; D015854:Up-Regulation
D006873:Hydroquinones; D017879:Isothiocyanates; D013454:Sulfoxides; D013861:Thiocyanates; C018855:2-tert-butylhydroquinone; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C016766:sulforaphane; D005978:Glutathione