Your browser doesn't support javascript.
loading
Inhibition of Janus activated kinase-3 protects against myocardial ischemia and reperfusion injury in mice
Experimental & Molecular Medicine ; : e23-2013.
Article in English | WPRIM | ID: wpr-159138
ABSTRACT
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.
Subject(s)

Full text: Available Index: WPRIM (Western Pacific) Main subject: Quinazolines / Myocardial Reperfusion Injury / Cell Movement / Apoptosis / Chemokines / Myocytes, Cardiac / Janus Kinase 3 / Heart Function Tests / Inflammation / Macrophages Limits: Animals Language: English Journal: Experimental & Molecular Medicine Year: 2013 Type: Article

Similar

MEDLINE

...
LILACS

LIS

Full text: Available Index: WPRIM (Western Pacific) Main subject: Quinazolines / Myocardial Reperfusion Injury / Cell Movement / Apoptosis / Chemokines / Myocytes, Cardiac / Janus Kinase 3 / Heart Function Tests / Inflammation / Macrophages Limits: Animals Language: English Journal: Experimental & Molecular Medicine Year: 2013 Type: Article