title: Expression of superoxide dismutase in hyperglycemic focal cerebral ischemia in the rat.
abstract: This study investigated the possibility that hyperglycemia induces early expression of various superoxide dismutases (SOD) and nitric oxide synthases (NOS) following focal cerebral ischemia in the rat. MnSOD, CuZnSOD, nNOS and eNOS mRNA and protein expression were examined 3 h after permanent middle cerebral artery occlusion under acute hyperglycemic or normoglycemic conditions. 2,3,5-triphenyltetrazolium chloride (TTC) treatment post-mortem revealed a significant area at risk of infarction following ischemia in hyperglycemic compared to normoglycemic rats. Although no changes in MnSOD, CuZnSOD, nNOS and eNOS mRNA expression were detected, Western blots of ischemic cortex revealed an increase in MnSOD and CuZnSOD protein expression in hyperglycemic compared to normoglycemic rats. Pre-treatment of hyperglycemic rats with the NOS inhibitors L-nitroarginine methyl ester (L-NAME) and 7-nitroindazole (7-NI) or dehydroascorbic acid (DHA), a superoxide scavenger, significantly reduced the TTC delineated zone. The hyperglycemia-induced post-transcriptional upregulation of MnSOD and CuZnSOD levels suggest a response to increased superoxide production which, in the presence of increased nitric oxide production, may play a major role in the increased risk of damage following hyperglycemic stroke.
authors.affiliation: Laboratoire de Neurobiologie, Centre de Recherche du CHUM, Hôpital St-Luc, A-466, 1058 St-Denis St, Montréal, Québec, Canada H2X 3J4. chanchan@globetrotter.net
authors.forename: Chantal
authors.initials: C
authors.lastname: Bémeur
authors.forename: Line
authors.initials: L
authors.lastname: Ste-Marie
authors.forename: Paul
authors.initials: P
authors.lastname: Desjardins
authors.forename: Roger F
authors.initials: RF
authors.lastname: Butterworth
authors.forename: Luc
authors.initials: L
authors.lastname: Vachon
authors.forename: Jane
authors.initials: J
authors.lastname: Montgomery
authors.forename: Alan S
authors.initials: AS
authors.lastname: Hazell
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002545:Brain Ischemia / Q000201:enzymology*; D003683:Dehydroascorbic Acid / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006943:Hyperglycemia / Q000201:enzymology*; D007150:Immunohistochemistry; D007191:Indazoles / Q000494:pharmacology; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D000199:Actins; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D007191:Indazoles; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D013482:Superoxide Dismutase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D003683:Dehydroascorbic Acid