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首页> 外文期刊>American Journal of Physiology >Protein kinase C and preconditioning: role of the sarcoplasmic reticulum.
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Protein kinase C and preconditioning: role of the sarcoplasmic reticulum.

机译：蛋白激酶C和预处理：肌浆网的作用。

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摘要

Activation of protein kinase C (PKC) is cardioprotective, but the mechanism(s) by which PKC mediates protection is not fully understood. Inasmuch as PKC has been well documented to modulate sarcoplasmic reticulum (SR) Ca2+ and because altered SR Ca2+ handling during ischemia is involved in cardioprotection, we examined the role of PKC-mediated alterations of SR Ca2+ in cardioprotection. Using isolated adult rat ventricular myocytes, we found that addition of 1,2-dioctanoyl-sn-glycerol (DOG), to activate PKC under conditions that reduced myocyte death associated with simulated ischemia and reperfusion, also reduced SR Ca2+. Cell death was 57.9 +/- 2.9% and 47.3 +/- 1.8% in untreated and DOG-treated myocytes, respectively (P < 0.05). Using fura 2 fluorescence to monitor Ca2+ transients and caffeine-releasable SR Ca2+, we examined the effect of DOG on SR Ca2+. Caffeine-releasable SR Ca2+ was significantly reduced (by approximately 65%) after 10 min of DOG treatment compared with untreated myocytes (P < 0.05). From our examination of the mechanism by which PKC alters SR Ca2+, we present the novel finding that DOG treatment reduced the phosphorylation of phospholamban (PLB) at Ser16. This effect is mediated by PKC-epsilon, because a PKC-epsilon-selective inhibitory peptide blocked the DOG-mediated decrease in phosphorylation of PLB and abolished the DOG-induced reduction in caffeine-releasable SR Ca2+. Using immunoprecipitation, we further demonstrated that DOG increased the association between protein phosphatase 1 and PLB. These data suggest that activated PKC-epsilon reduces SR Ca2+ content through PLB dephosphorylation and that reduced SR Ca2+ may be important in cardioprotection.
机译：蛋白激酶C（PKC）的激活具有心脏保护作用，但是尚未完全了解PKC介导保护的机制。由于PKC已被充分证明可以调节肌浆网（SR）Ca2 +，并且由于缺血期间SR Ca2 +处理的改变与心脏保护有关，因此我们研究了PKC介导的SR Ca2 +改变在心脏保护中的作用。使用分离的成年大鼠心室肌细胞，我们发现添加1,2-二辛酰基-sn-甘油（DOG）在降低与模拟缺血和再灌注相关的心肌细胞死亡的条件下激活PKC，也降低了SR Ca2 +。在未经处理和经DOG处理的心肌细胞中，细胞死亡分别为57.9 +/- 2.9％和47.3 +/- 1.8％（P <0.05）。使用呋喃2荧光监测Ca2 +瞬态和咖啡因释放的SR Ca2 +，我们研究了DOG对SR Ca2 +的影响。与未经处理的心肌细胞相比，DOG处理10分钟后，可释放咖啡因的SR Ca2 +明显降低（降低了约65％）（P <0.05）。从我们对PKC改变SR Ca2 +的机理的研究中，我们提出了一个新发现，即DOG处理可降低Ser16的磷酸lamban（PLB）的磷酸化。此作用是由PKCε介导的，因为PKCε选择性抑制肽阻止了DOG介导的PLB磷酸化的减少，并消除了DOG诱导的咖啡因释放的SR Ca2 +降低。使用免疫沉淀，我们进一步证明DOG增加了蛋白磷酸酶1和PLB之间的关联。这些数据表明，活化的PKC-ε通过PLB脱磷酸作用降低了SR Ca2 +的含量，并且降低的SR Ca2 +在心脏保护中可能很重要。

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