High molecular weight FGF-2 promotes postconditioning-like cardioprotection linked to activation of the protein kinase C isoforms Akt and p70 S6 kinase
High molecular weight FGF-2 promotes postconditioning-like cardioprotection linked to activation of the protein kinase C isoforms Akt and p70 S6 kinase
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DOI：
10.1139/y09-049
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发表时间：
2009-10-01
影响因子：
2.1
通讯作者：
Kardami, Elissavet
中科院分区：
文献类型：
--
作者：
Jiang, Zhi-Sheng;Wen, Ge-Bo;Kardami, Elissavet
成纤维细胞生长因子2（FGF-2）是一种多功能蛋白质，翻译为高分子量和低分子量同种型（分别为hi-和lo-FGF-2）。虽然lo-FGF-2（18 kDa）的后处理心脏保护作用已被证明，但hi-FGF-2的研究较少。我们使用所有离体灌注的缺血-再灌注大鼠心脏模型来研究缺血后（再灌注期间）给予hi-FGF-2对收缩功能恢复和组织挽救的作用，如细胞溶质细胞色素c水平降低所示。与溶剂处理组相比，hi-FGF-2处理的心脏具有显著改善的收缩压恢复、发展压、收缩和舒张速率以及冠状动脉流量，以及降低的细胞溶质细胞色素c的相对水平。hi-FGF-2对功能恢复和细胞溶质细胞色素c的影响与lo-FGF-2诱导的影响无法区分。hi-和lo-FGF-2均上调磷酸化（活化）Akt和p70 S6激酶的相对水平，并且它们均促进蛋白激酶C（PKC）的α、β和ζ亚型易位至再灌注心脏的颗粒部分。然而，hi-FGF-2组对PKC zeta和p70 S6激酶的影响程度明显强于lo-FGF-2组。我们的结论是，急性缺血后心脏保护高或低FGF-2是亚型非特异性的，可能是由PKC和Akt介导的。尽管如此，p70 S6和PKC zeta对hi-FGF-2的敏感性增强提示了亚型特异性功能。
Fibroblast growth factor 2 (FGF-2) is a multifunctional protein translated as high and low molecular weight isoforms (hi- and lo-FGF-2, respectively). Although the postconditioning cardioprotective effect of lo-FGF-2 (18 kDa) has been documented, hi-FGF-2 is less well studied. We used ail isolated perfused rat heart model of ischemia-reperfusion to study the effects of postischemic (during, reperfusion) administration of hi-FGF-2 on recovery of contractile function and tissue salvage, as indicated by decreased cytosolic cytochrome c levels. Compared with the vehicle-treated group, hi-FGF-2-treated hearts had significantly improved recovery of systolic pressure, developed pressure, rates of contraction and relaxation, and coronary flow, as well as decreased relative levels of cytosolic cytochrome c. The effects of hi-FGF-2 on functional recovery and cytosolic cytochrome c were indistinguishable from those induced by lo-FGF-2. Both hi- and lo-FGF-2 upregulated relative levels of phosphorylated (activated) Akt and p70 S6 kinase, and they both promoted translocation of alpha, epsilon, and zeta isoforms of protein kinase C (PKC) to the particulate fraction of reperfused hearts. The magnitude of the effect on PKC zeta and p70 S6 kinases, however, was significantly more potent in the hi-FGF-2 than in the lo-FGF-2 group. We conclude that acute postischemic cardioprotection by hi- or lo-FGF-2 is isoform nonspecific and likely to be mediated by PKC and Akt. Nevertheless, isoform-specific functions are suggested by the augmented sensitivity of p70 S6 and PKC zeta to hi-FGF-2.