title: Epinephrine upregulates superoxide dismutase in human coronary artery endothelial cells.
abstract: Regular exercise resulting in release of catecholamines is an oxidant stress, and yet it protects humans from acute cardiac events. We designed this study to examine the effect of epinephrine on free radical release and endogenous superoxide dismutase (SOD) gene and protein expression in human coronary artery endothelial cells (HCAECs). HCAECs were incubated with epinephrine (10(-9) to 10(-5) M) alone or with the water-soluble analog of vitamin E (trolox) (10(-5) M), the lipid-soluble vitamin E (5 x 10(-5) M), or the beta(1)-adrenergic blocker atenolol (10(-5) M). At 1 and 24 h of incubation with epinephrine, superoxide anion generation increased by 102 and 81% in the HCAECs. There was a marked increase in both MnSOD and Cu/ZnSOD mRNA and protein, as determined by RT-PCR and Western Analysis, respectively. Both MnSOD and Cu/ZnSOD activities were also increased. Pretreatment of HCAECs with trolox and vitamin E decreased superoxide anion generation (p <.05 vs. epinephrine alone) and blocked the subsequent upregulation of SOD mRNA and protein. Treatment of cells with the beta-blocker atenolol also blocked the upregulation of SOD (p <.05 vs. epinephrine alone). These observations suggest that epinephrine via beta(1)-adrenoceptor activation causes superoxide anion generation, and the superoxide subsequently upregulates the endogenous antioxidant species SOD. These observations may be the basis of long-term benefits of exercise.
authors.affiliation: Department of Medicine, University of Florida College of Medicine and VA Medical Center, Gainesville, FL, USA. MehtaJL@UAMS.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Mehta
authors.forename: D
authors.initials: D
authors.lastname: Li
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002839:Chromans; D012333:RNA, Messenger; D013481:Superoxides; D014810:Vitamin E; D001262:Atenolol; D013482:Superoxide Dismutase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D004837:Epinephrine