کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10954273 | 1097883 | 2007 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The cardioprotective effect of the low molecular weight isoform of fibroblast growth factor-2: The role of JNK signaling
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
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![عکس صفحه اول مقاله: The cardioprotective effect of the low molecular weight isoform of fibroblast growth factor-2: The role of JNK signaling The cardioprotective effect of the low molecular weight isoform of fibroblast growth factor-2: The role of JNK signaling](/preview/png/10954273.png)
چکیده انگلیسی
Our laboratory showed that overexpression of fibroblast growth factor-2 (FGF2) protected the heart against ischemia-reperfusion injury. FGF2 has different protein isoforms (low [LMW] and high [HMW] molecular weight isoforms) produced from alternative translation start sites. However, which FGF2 isoform(s) mediates this cardioprotection, and which signaling pathway (i.e., mitogen-activated protein kinase (MAPK)) elicits FGF2 isoform-induced cardioprotection remains to be elucidated. Methods and results: Wildtype, Fgf2 KO (absence of all FGF2 isoforms) and FGF2 LMWKO (absence of LMW isoform) hearts were subjected to an ex vivo work-performing heart ischemic model of 60 min ischemia and 120 min reperfusion. There was a significant decrease in the recovery of post-ischemic contractile function (p < 0.05) in Fgf2 KO and FGF2 LMWKO mouse hearts compared to wildtype hearts. Following ischemia-reperfusion injury, MKK4/7, JNK, and c-Jun were significantly phosphorylated (i.e., activated), and the levels of TUNEL-positive nuclei and caspase 3 cleavage were significantly increased in vehicle-treated Fgf2 KO and FGF2 LMWKO compared to wildtype hearts (p < 0.05). A novel JNK pathway inhibitor, CEP11004 (50 nM), significantly restored the post-ischemic contractile function and reduced myocardial cell death, as measured by CK release and apoptotic markers, compared to DMSO-treated cohorts (p < 0.05). Overall, our data indicate that the LMW isoform has an important role in restoring cardiac function after ischemia-reperfusion (I/R) injury. These results provide unequivocal evidence that inhibition of JNK signaling is involved in FGF2 LMW isoform-mediated cardioprotection and that the potential mechanism may be through inhibition of the apoptotic process.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 42, Issue 1, January 2007, Pages 106-120
Journal: Journal of Molecular and Cellular Cardiology - Volume 42, Issue 1, January 2007, Pages 106-120
نویسندگان
Siyun Liao, Darius Porter, Alana Scott, Gilbert Newman, Thomas Doetschman, Jo El J. Schultz,