Heat shock-induced manganese superoxide dismutase enhances the tolerance of cardiac myocytes to hypoxia-reoxygenation injury.
We evaluated the mechanism of the heat shock-induced tolerance to ischemia-reperfusion using a model of hypoxia-reoxygenation tolerance in neonatal rat cardiac myocytes. Myocytes exposed to heat shock (42 degrees C, 1 h) exhibited a 1.8-fold increase in levels of manganese superoxide dismutase (Mn-SOD) mRNA after 40 min v control cells. The concentration of Mn-SOD increased from 0.49+/-0.04 microg/mg protein to 0.68+/-0.05 microg/mg protein after 24 h (P<0. 05). Levels of heat shock protein 72 (hsp72; inducible form) mRNA and protein also increased markedly after heat shock exposure. The release of creatine kinase (CK) from the myocytes and the depletion of ATP level in the myocytes exposed to hypoxia (pO2: 7 mmHg, 3 h) and reoxygenation (pO2: 143 mmHg) were significantly reduced following heat shock pretreatment (CK: 1.18+/-0.14 U/l v 0.62+/-0.13 U/l, ATP: 11.9+/-1.1 nmol/mg protein v 16.2+/-1.0 nmol/mg protein, P<0.05). Treatment with antisense oligodeoxyribonucleotides to Mn-SOD (1.5 micromol/l) completely inhibited the heat shock-associated induction of Mn-SOD (0.47+/-0.05 microg/mg protein), but not hsp72, and abolished the heat shock-induced decrease in CK release (1.04+/-0.15 U/l, P<0.05) and depletion of ATP level (11. 2+/-1.1 nmol/mg protein, P<0.05). Results indicate that Mn-SOD induction, not hsp72 induction, plays a pivotal role in the heat shock-induced acquisition of tolerance to hypoxia-reoxygenation in neonatal rat cardiac myocytes.
Yamashita
N
N
First Department of Medicine, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565, Japan.
Hoshida
S
S
Nishida
M
M
Igarashi
J
J
Taniguchi
N
N
Tada
M
M
Kuzuya
T
T
Hori
M
M
D000818:Animals; D000831:Animals, Newborn; D004790:Enzyme Induction; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018882:Heat Stress Disorders / Q000378:metabolism*; D008345:Manganese; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011921:Rats, Inbred WKY; D015427:Reperfusion Injury / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000502:physiology*
D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D008345:Manganese; D013482:Superoxide Dismutase