首页> 外文期刊>American Journal of Physiology >alpha-Adrenergic response and myofilament activity in mouse hearts lacking PKC phosphorylation sites on cardiac TnI.
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alpha-Adrenergic response and myofilament activity in mouse hearts lacking PKC phosphorylation sites on cardiac TnI.

机译:缺少心脏TnI上PKC磷酸化位点的小鼠心脏中的α-肾上腺素反应和肌丝活性。

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摘要

Protein kinase C (PKC)-mediated phosphorylation of cardiac myofilament (MF) proteins has been shown to depress the actomyosin interaction and may be important during heart failure. Biochemical studies indicate that phosphorylation of Ser(43) and Ser(45) of cardiac troponin I (cTnI) plays a substantial role in the PKC-mediated depression. We studied intact and detergent-extracted papillary muscles from nontransgenic (NTG) and transgenic (TG) mouse hearts that express a mutant cTnI (Ser43Ala, Ser45Ala) that lacks specific PKC-dependent phosphorylation sites. Treatment of NTG papillary muscles with phenylephrine (PE) resulted in a transient increase and a subsequent 62% reduction in peak twitch force. TG muscles showed no transient increase and only a 45% reduction in force. There was a similar difference in maximum tension between NTG and TG fiber bundles that had been treated with a phorbol ester and had received subsequent detergent extraction. Although levels of cTnI phosphorylation correlated with these differences, the TG fibers also demonstrated a decrease in phosphorylation of cardiac troponin T. The PKC-specific inhibitor chelerythrine inhibited these responses. Our data provide evidence that specific PKC-mediated phosphorylation of Ser(43) and Ser(45) of cTnI plays an important role in regulating force development in the intact myocardium.
机译:已证明蛋白激酶C(PKC)介导的心肌肌丝(MF)蛋白磷酸化可抑制肌动球蛋白相互作用,并且在心力衰竭期间可能很重要。生化研究表明,心肌肌钙蛋白I(cTnI)的Ser(43)和Ser(45)的磷酸化在PKC介导的抑郁中起重要作用。我们研究了表达缺失突变体cTnI(Ser43Ala,Ser45Ala)而缺乏特定PKC依赖的磷酸化位点的非转基因(NTG)和转基因(TG)小鼠心脏的完整乳胶和去污剂提取的乳头肌。用去氧肾上腺素(PE)治疗NTG乳头肌导致瞬时增加,峰值抽搐力随之降低62%。 TG肌肉没有瞬时增加,而力量仅减少了45%。用佛波酯处理过的NTG和TG纤维束之间的最大张力之间存在相似的差异,随后又接受了洗涤剂的萃取。尽管cTnI磷酸化水平与这些差异相关,但TG纤维还显示出心肌肌钙蛋白T磷酸化的降低。PKC特异性抑制剂白屈菜红碱抑制了这些反应。我们的数据提供了证据,即特定PKC介导的cTnI的Ser(43)和Ser(45)的磷酸化在调节完整心肌的力发展中起着重要作用。

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