Hypoxic stress induces cardiotrophin-1 expression in cardiac myocytes.
Cardiotrophin-1 (CT-1), a novel cytokine that belongs to the interleukin-6 cytokine family, activates gp130 dependent signaling pathway to transduce hypertrophic and cytoprotective signals in cardiac myocytes. To investigate the pathophysiological significance of CT-1 in myocardial disease, the expression of CT-1 was examined after hypoxic stimulation in cardiac myocytes. Highly expressed CT-1 mRNA was observed in embryonic and adult hearts by RNase protection assay. Cardiac myocytes subjected to hypoxic stimulation augmented CT-1 mRNA expression. Although CT-1 mRNA was expressed to a higher extent in non-myocardial cells, the expression was not affected with the stimulation. Conditioned medium from cultured cardiac myocytes presented the ability to tyrosine phosphorylate STAT3 through gp130 and that was further augmented with hypoxic conditioned medium. These results demonstrated for the first time that CT-1 expression is augmented after hypoxic stimulation and hypoxic conditioned medium presented enhanced ability to activate STAT3 in cardiac myocytes. CT-1 might play an important role in the pathogenesis of ischemic heart disease.
Hishinuma
S
S
Department of Molecular Medicine, Osaka University Medical School, Suita, Osaka, 565-0871, Japan.
Funamoto
M
M
Fujio
Y
Y
Kunisada
K
K
Yamauchi-Takihara
K
K
D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism / Q000494:pharmacology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D006321:Heart / Q000196:embryology; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D017077:Culture Media, Conditioned; D016207:Cytokines; D004268:DNA-Binding Proteins; C494200:Il6st protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; C092073:cardiotrophin 1