Involvement of adrenergic pathways in activation of catalase by myocardial ischemia-reperfusion.
In situ rabbit hearts were subjected to 15 min of regional myocardial ischemia, and at various time points of reperfusion, antioxidant enzyme activity and mRNA expression were measured in ischemic and nonischemic myocardium. Catalase activity increased significantly in both ischemic and nonischemic myocardium, peaking at 1 h after reperfusion and then gradually returning to the control level. Northern blot analysis showed enhanced expression of catalase mRNA in both areas. There were no changes in redox status, because glutathione levels were not altered by ischemia-reperfusion (I/R). We also tested whether catalase activation in the heart results from signaling pathways that might influence not only the heart but also other organs. We found that catalase activity in the brain was increased after myocardial I/R and ischemic stress to the intestine was equipotent to myocardial I/R in catalase activation. We next sought to elucidate the possible involvement of the adrenergic system in catalase stimulation induced by ischemic stimuli. After pretreatment with the alpha-adrenergic receptor antagonist prazosin, I/R failed to increase catalase activity in the heart and brain. Intravenous norepinephrine increased catalase activity in the heart, brain, and liver. This study shows that brief I/R activates a signaling mechanism to induce catalase activation in multiple organs and the alpha-adrenergic system is involved as an intermediate pathway in this signal transmission.
Kim
Young-Hoon
YH
Department of Pharmacology, College of Medicine, University of Ulsan, Seoul 138-736, Korea.
Chun
Yang-Sook
YS
Park
Jong-Wan
JW
Kim
Chan-Hyung
CH
Kim
Myung-Suk
MS
D000320:Adrenergic Fibers / Q000502:physiology*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D005978:Glutathione / Q000378:metabolism; D007422:Intestines / Q000098:blood supply; D007511:Ischemia / Q000503:physiopathology; D008099:Liver / Q000201:enzymology; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism; D009434:Neural Pathways / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D012333:RNA, Messenger; D010088:Oxidoreductases; D002374:Catalase; D005978:Glutathione; D009638:Norepinephrine; D011224:Prazosin