Activation of JAK/STAT pathway transduces cytoprotective signal in rat acute myocardial infarction

Shinji Negoro, Keita Kunisada, Eiroh Tone, Masanobu Funamoto, Hidemasa Oh, Tadamitsu Kishimoto, Keiko Yamauchi-Takihara

Research output: Contribution to journalArticle

172 Citations (Scopus)

Abstract

Objectives: We reported that the activation of gp130 transduced hypertrophic and cytoprotective signals via Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway in cardiac myocytes. Recent in vivo experiments have demonstrated that the JAK/STAT pathway is activated in acute pressure overload hearts. The present study was designed to examine whether the JAK/STAT pathway is also activated in acute myocardial infarction (AMI) and to determine its pathophysiological roles in ischemic heart disease. Methods and results: AMI model was generated by the ligation of proximal left anterior descending coronary artery of male Wistar rat. They were sacrificed at various time points ranging from 1 to 24 h after coronary ligation and their hearts were examined. Tyrosine phosphorylation of STAT3 was observed in the myocardium obtained from both the ischemic area and the healthy border area adjacent to the infarcted area. The AMI rats were next randomly assigned to two groups, one with coronary ligation only (group M), and the other with coronary ligation with AG-490 treatment (1 mg/kg i.v., every 4 h), a specific JAK2 inhibitor (group A). In group A, phosphorylation of STAT3 was significantly suppressed and caspase-3 activity and Bax expression were significantly increased in the myocardium after AMI. In group M, few apoptotic myocytes were identified in the border area by means of TUNEL assay. However, a significant increase in apoptotic cells was observed in group A. Conclusions: Administration of JAK2 inhibitor resulted in deterioration of myocardial viability in AMI hearts. The JAK/STAT pathway is activated in AMI myocardium and plays a pivotal role in cytoprotective signaling. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)797-805
Number of pages9
JournalCardiovascular Research
Volume47
Issue number4
DOIs
Publication statusPublished - Sep 1 2000
Externally publishedYes

Keywords

  • Apoptosis
  • Cytokines
  • Infarction
  • Signal transduction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Negoro, S., Kunisada, K., Tone, E., Funamoto, M., Oh, H., Kishimoto, T., & Yamauchi-Takihara, K. (2000). Activation of JAK/STAT pathway transduces cytoprotective signal in rat acute myocardial infarction. Cardiovascular Research, 47(4), 797-805. https://doi.org/10.1016/S0008-6363(00)00138-3