Role of lipid rafts in ceramide and nitric oxide signaling in the ischemic and preconditioned hearts
Role of lipid rafts in ceramide and nitric oxide signaling in the ischemic and preconditioned hearts
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DOI：
10.1016/j.yjmcc.2005.10.005
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发表时间：
2006-02-01
影响因子：
5
通讯作者：
Das, DK
中科院分区：
文献类型：
--
作者：
Der, P;Cui, JH;Das, DK
一氧化氮在心肌缺血再灌注损伤和心肌对缺血应激的适应中起着至关重要的作用。为了了解缺血心肌中一氧化氮行为的二分法，对离体大鼠心脏进行了缺血再灌注处理。采用高效薄层色谱法（HPTLC）测定组织中鞘磷脂（SM）、神经酰胺和鞘磷脂的含量。用caveolin-1特异性抗体免疫沉淀心肌血浆蛋白。缺血/再灌注导致SM分解，神经酰胺和鞘氨醇相应积累。eNOS特异性抗体免疫沉淀显示eNOS与心脏小窝蛋白-1分数的关联。缺血/再灌注引起收缩功能的抑制，凋亡细胞死亡和心肌梗死面积的增加，这可以通过给心脏预灌注地西帕明逆转，地西帕明是一种鞘磷脂酶抑制剂，也可以阻止神经酰胺的积累和eNOS与caveolin-1的关联。通过反复的可逆缺血再灌注，使心脏适应缺血应激，得到了类似的结果。结果表明，缺血/再灌注导致eNOS增加，而eNOS由于与caveolin-1结合而无法进入缺血心脏。神经酰胺在这一过程中起着至关重要的作用，因为通过心肌适应缺血或使用地西帕明来预防神经酰胺的形成，可以抑制eNOS与caveolin-1的关联，从而减轻心肌缺血再灌注损伤。(c) 2005 Elsevier Ltd版权所有。
Nitric oxide plays a crucial role in myocardial ischemia reperfusion injury as well as in myocardial adaptation to ischemic stress. To understand the dichotomy of nitric oxide behavior in the ischemic myocardium, isolated rat hearts were subjected to ischemia/reperfusion protocol. The tissue contents of sphingomyelin (SM), ceramide and sphingosine were determined by high performance thin layer chromatography (HPTLC). The myocardial plasma proteins were immunoprecipitated with caveolin-1 specific antibody. Ischemia/reperfusion resulted in the breakdown of SM with corresponding accumulation of ceramide and sphingosine. Immunoprecipitation with eNOS-specific antibody revealed the association of eNOS with caveolin-1 Fraction of the heart. Ischemia/reperfusion Caused a depression of contractile function and an increased apoptotic cell death and myocardial infarct size, which were reversed by preperfusing the hearts with desipramine, an sphingomyelinase inhibitor that also prevented ceramide accumulation and eNOS association with caveolin-1. The similar results were obtained when the hearts, were adapted to ischemic stress by subjecting them to repeated reversible ischemia and reperfusion. The results indicate that ischemia/reperfusion causes an increase in eNOS, which is unavailable to the ischemic heart because of its binding with caveolin-1. Ceramide plays a crucial role in this process, because prevention of ceramide formation either by myocardial adaptation to ischemia or with desipramine results in the inhibition of eNOS association with caveolin-1 thereby reducing myocardial ischemic reperfusion injury. (c) 2005 Elsevier Ltd. All rights reserved.