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KMID : 0620920130450050005
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Experimental & Molecular Medicine
2013 Volume.45 No. 5 p.5 ~ p.0
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Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice
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Oh Young-Bin
Ahn Min
Lee Sang-Myeong
Koh Hyoung-Won
Lee Sun-Hwa
Kim Suhn-Hee
Park Byung-Hyun
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Abstract
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Recent studies have documented that Janus-activated kinase (JAK)?signal transducer and activator of transcription (STAT) pathway can modulate the apoptotic program in a myocardial ischemia/reperfusion (I/R) model. To date, however, limited studies have examined the role of JAK3 on myocardial I/R injury. Here, we investigated the potential effects of pharmacological JAK3 inhibition with JANEX-1 in a myocardial I/R model. Mice were subjected to 45?min of ischemia followed by varying periods of reperfusion. JANEX-1 was injected 1?h before ischemia by intraperitoneal injection. Treatment with JANEX-1 significantly decreased plasma creatine kinase and lactate dehydrogenase activities, reduced infarct size, reversed I/R-induced functional deterioration of the myocardium and reduced myocardial apoptosis. Histological analysis revealed an increase in neutrophil and macrophage infiltration within the infarcted area, which was markedly reduced by JANEX-1 treatment. In parallel, in in vitro studies where neutrophils and macrophages were treated with JANEX-1 or isolated from JAK3 knockout mice, there was an impairment in the migration potential toward interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), respectively. Of note, however, JANEX-1 did not affect the expression of IL-8 and MCP-1 in the myocardium. The pharmacological inhibition of JAK3 might represent an effective approach to reduce inflammation-mediated apoptotic damage initiated by myocardial I/R injury.
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KEYWORD
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apoptosis, infiltration, ischemia/reperfusion, JAK3, JANEX-1
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