Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hypoxia/reoxygenation-induced oxidative stress through the upregulation of manganese superoxide dismutase

Citation
S. Negoro et al., Activation of signal transducer and activator of transcription 3 protects cardiomyocytes from hypoxia/reoxygenation-induced oxidative stress through the upregulation of manganese superoxide dismutase, CIRCULATION, 104(9), 2001, pp. 979-981
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
CIRCULATION
ISSN journal
0009-7322 → ACNP
Volume
104
Issue
9
Year of publication
2001
Pages
979 - 981
Database
ISI
SICI code
0009-7322(20010828)104:9<979:AOSTAA>2.0.ZU;2-B
Abstract
Background-Mice with cardiac-specific overexpression. of signal transducer and activator of transcription 3 (STAT3) are resistant to doxorubicin-induc ed damage. The STAT3 signal may be involved in the detoxification of reacti ve oxygen species (ROS). Methods and Results-The effects of leukemia inhibitory factor (LIF) or aden ovirus-mediated transfection. of constitutively activated STAT3 (caSTAT3) o n the intracellular ROS formation induced by hypoxia/reoxygenation (H/R) we re examined using rat neonatal cardiomyocytes. Either LIF treatment or caST AT3 significantly suppressed the increase of H/R-induced ROS evaluated by 2 ',7'-dichlorofluorescin diacetate fluorescence. To assess whether ROS are r eally involved in H/R-induced cardiomyocyte injury, the amount of creatine phosphokinase in cultured medium was examined. Both LIF treatment and caSTA T3 significantly decreased H/R-induced creatine phosphokinase release. Thes e results indicate that the gp130/STAT3 signal protects H/R-induced cardiom yocyte injury by scavenging ROS generation. To investigate the mechanism of scavenging ROS, the effects of LIF on the induction of antioxidant enzymes were examined. LIF treatment significantly increased the expression of man ganese superoxide dismutase (MnSOD) mRNA, whereas the expression of the cat alase and glutathione peroxidase genes were unaffected. This induction of M nSOD mRNA expression was completely blocked by adenovirus-mediated transfec tion of dominant-negative STAT3. Moreover, caSTAT3 augmented MnSOD mRNA and its enzyme activity. In addition, the antisense oligodeoxyribonucleotide t o MnSOD significantly inhibited both LIF and caSTAT3-mediated protective ef fects. Conclusions-The activation of STAT3 induces a protective effect on H/R-indu ced cardiomyocyte damage, mainly by inducting MnSOD. The STAT3-mediated sig nal is proposed as a therapeutical target of ROS-induced cardiomyocyte inju ry.