INDUCTION OF MANGANESE SUPEROXIDE-DISMUTASE IN RAT CARDIAC MYOCYTES INCREASES TOLERANCE TO HYPOXIA 24 HOURS AFTER PRECONDITIONING

Citation
N. Yamashita et al., INDUCTION OF MANGANESE SUPEROXIDE-DISMUTASE IN RAT CARDIAC MYOCYTES INCREASES TOLERANCE TO HYPOXIA 24 HOURS AFTER PRECONDITIONING, The Journal of clinical investigation, 94(6), 1994, pp. 2193-2199
Citations number
55
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Medicine, Research & Experimental
ISSN journal
0021-9738
Volume
94
Issue
6
Year of publication
1994
Pages
2193 - 2199
Database
ISI
SICI code
0021-9738(1994)94:6<2193:IOMSIR>2.0.ZU;2-T
Abstract
Manganese superoxide dismutase (Mn-SOD) is induced in ischemic hearts 24 h after ischemic preconditioning, when tolerance to ischemia is acq uired. We examined the relationship between Mn-SOD induction and the p rotective effect of preconditioning using cultured rat cardiac myocyte s. Exposure of cardiac myocytes to brief hypoxia (1 h) decreased creat ine kinase release induced by sustained hypoxia (3 h) that follows whe n the sustained hypoxia was applied 24 h after hypoxic preconditioning (57% of that in cells without preconditioning). The activity and cont ent of Mn-SOD in cardiac myocytes were increased 24 h after hypoxic pr econditioning (activity, 170%; content, 139% compared with cells witho ut preconditioning) coincidentally with the acquisition of tolerance t o hypoxia. Mn-SOD mRNA was also increased 20-40 min after precondition ing. Antisense oligodeoxyribonucleotides corresponding to the initiati on site of Mn-SOD translation inhibited the increases in the Mn-SOD co ntent and activity and abolished the expected decrease in creatine kin ase release induced by sustained hypoxia after 24 h of hypoxic precond itioning. Sense oligodeoxyribonucleotides did not abolish either Mn-SO D induction or tolerance to hypoxia. These results suggest that the in duction of Mn-SOD in myocytes by preconditioning plays a pivotal role in the acquisition of tolerance to ischemia at a later phase (24 h) of ischemic preconditioning.