First molecular evidence that inositol trisphosphate signaling contributes to infarct size reduction with preconditioning.
First molecular evidence that inositol trisphosphate signaling contributes to infarct size reduction with preconditioning.
复制标题
第一个分子证据表明肌醇三磷酸信号传导有助于通过预处理减少梗塞面积。
DOI：
10.1152/ajpheart.00313.2006
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Whittaker,Peter
中科院分区：
文献类型：
--
作者：
Przyklenk,Karin;Maynard,Michelle;Whittaker,Peter
Considerable attention has focused on the role of protein kinase C (PKC) in triggering the profound infarct-sparing effect of ischemic preconditioning (PC). In contrast, the involvement of inositol 1,4,5-trisphosphate [Ins(,,)P3], the second messenger generated in parallel with the diacylglycerol-PKC pathway, remains poorly understood. We hypothesized that, if Ins(,,)P3signaling [i.e., release of Ins(,,)P3and subsequent binding to Ins(,,)P3receptors] contributes to PC-induced cardioprotection, then the reduction of infarct size achieved with PC would be attenuated in mice that are deficient in Ins(,,)P3receptor protein. To test this concept, hearts were harvested from1) B6C3Fe-a/a-Itpr-1opt+/−/Jmutants displaying reduced expression of Ins(,,)P3receptor-1 protein,2)Itpr-1opt+/+wild types from the colony, and3) C57BL/6J mice. All hearts were buffer-perfused and randomized to receive two 5-min episodes of PC ischemia, pretreatment withd-myo-Ins(,,)P3[sodium salt of native Ins(,,)P3], the mitochondrial ATP-sensitive K+channel opener diazoxide, or no intervention (controls). After the treatment phase, all hearts underwent 30-min global ischemia followed by 2 h of reperfusion, and infarct size was delineated by tetrazolium staining. In both wild-type and C57BL/6J cohorts, area of necrosis in hearts that received PC,d-myo-Ins(,,)P3, and diazoxide averaged 28–35% of the total left ventricle (LV), significantly smaller than the values of 52–53% seen in controls (P< 0.05). In contrast, inItpr-1opt+/−mutants, protection was only seen with diazoxide: neither PC nord-myo-Ins(,,)P3limited infarct size (52–58% vs. 56% of the LV in mutant controls). These data provide novel evidence that Ins(,,)P3signaling contributes to infarct size reduction with PC.
