首页> 外文期刊>American Journal of Physiology >Alpha1-adrenoceptor-Gq-RhoA signaling is upregulated to increase myofibrillar Ca2+ sensitivity in failing hearts.
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Alpha1-adrenoceptor-Gq-RhoA signaling is upregulated to increase myofibrillar Ca2+ sensitivity in failing hearts.

机译:Alpha1-肾上腺素受体-Gq-RhoA信号被上调,以增加心脏衰竭患者的肌原纤维Ca2 +敏感性。

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摘要

Alpha1-adrenergic stimulation, coupled to Gq, has been shown to promote heart failure. However, the role of alpha1-adrenergic signaling in the regulation of myocardial contractility in failing myocardium is still poorly understood. To investigate this, we observed 1) the effect of phenylephrine on myofibrillar Ca2+ sensitivity in alpha-toxin-skinned cardiomyocytes, and 2) protein expression of Gq, RhoA, and myosin light chain phosphorylation using tachypacing-induced canine failing hearts. Phenylephrine significantly increased myofibrillar Ca2+ sensitivity in failing but not in normal cardiomyocytes. Whereas Y-27632 (Rho kinase inhibitor) blocked the phenylephrine-induced Ca2+ sensitization in the failing myocytes, calphostin C (protein kinase C inhibitor) had no effect on Ca2+ sensitization. The protein expression of Galpha(q) and RhoA and the phosphorylation level of regulatory myosin light chain significantly increased in the failing myocardium. Our results suggest that alpha1-adrenoceptor-Gq signaling is upregulated in the failing myocardium to increase the myofibrillar Ca2+ sensitivity mainly through the RhoA-Rho kinase pathway rather than through the protein kinase C pathway.
机译:研究表明,与Gq偶联的Alpha1-肾上腺素能刺激可导致心力衰竭。然而,α1-肾上腺素能信号传导在衰竭心肌中调节心肌收缩力的作用仍知之甚少。为了研究这一点,我们观察到1)苯肾上腺素对α-毒素皮肤的心肌细胞对肌原纤维Ca2 +敏感性的影响,以及2)使用速激肽诱导的犬衰竭心脏使Gq,RhoA和肌球蛋白轻链磷酸化的蛋白表达。肾上腺素在衰竭时可显着增加肌原纤维Ca2 +敏感性,但在正常心肌细胞中则不会。 Y-27632(Rho激酶抑制剂)阻断了去氧肾上腺素诱导的衰竭心肌细胞中Ca2 +致敏,而钙磷蛋白C(蛋白激酶C抑制剂)对Ca2 +致敏没有影响。在衰竭的心肌中,Galpha(q)和RhoA的蛋白质表达和调节性肌球蛋白轻链的磷酸化水平显着增加。我们的结果表明,α1-肾上腺素受体-Gq信号在衰竭的心肌中被上调,从而主要通过RhoA-Rho激酶途径而非蛋白激酶C途径增加肌原纤维Ca2 +敏感性。

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