...
首页> 外文期刊>Cell biology international. >β 2-Adrenergic receptor-induced transactivation of epidermal growth factor receptor and platelet-derived growth factor receptor via Src kinase promotes rat cardiomyocyte survival
【24h】

β 2-Adrenergic receptor-induced transactivation of epidermal growth factor receptor and platelet-derived growth factor receptor via Src kinase promotes rat cardiomyocyte survival

机译:β2-肾上腺素能受体通过Src激酶诱导的表皮生长因子受体和血小板源性生长因子受体的反式激活促进大鼠心肌细胞的存活

获取原文
获取原文并翻译 | 示例
           

摘要

Chronic stimulation of the β-AR (adrenergic receptor) promotes apoptosis of cardiomyocytes, which is implicated in cardiac dysfunction. β 1-AR and β 2-AR are the main subtypes of β-AR that exert distinct effects on the survival of cardiomyocytes. To clarify the physiological roles of β 1-AR and β 2-AR in cardiomyocytes, the effects of β 1-AR or β 2-AR knockdown on the survival of H9c2 cardiomyocytes was investigated. Knockdown of β 2-AR, but not β 1-AR, suppressed the phosphorylation of EGFR (epidermal growth factor receptor) and PDGFR (platelet-derived growth factor receptor) induced by ISO (isoprenaline). The EGFR inhibitor, AG1478, attenuated ERK (extracellular-signal-regulated kinase) activation and partially decreased cell survival. Pretreatment with AG1296, a PDGFR inhibitor, abolished ISO-induced Akt (also known as protein kinase B) phosphorylation and led to a decrease in cell viability. In addition, the Src tyrosine kinase inhibitor, PP2, blocked ISO-mediated both Akt and ERK activation and heavily suppressed viability. Accordingly, in primary neonatal rat cardiomyocytes, the β 2-AR inhibitor, but not the β 1-AR inhibitor, abrogated the transactivation of EGFR and PDGFR, which was respectively related to Akt and ERK activation. The results show that β 2-AR transactivates PDGFR and EGFR, thereby promoting survival of cardiomyocytes.
机译:慢性刺激β-AR(肾上腺素能受体)可促进心肌细胞凋亡,这与心脏功能障碍有关。 β1-AR和β2-AR是β-AR的主要亚型,对心肌细胞的存活有明显的影响。为了阐明β1-AR和β2-AR在心肌细胞中的生理作用,研究了β1-AR或β2-AR敲低对H9c2心肌细胞存活的影响。敲低β2-AR而不是β1-AR抑制了ISO(异戊二烯)诱导的EGFR(表皮生长因子受体)和PDGFR(血小板衍生的生长因子受体)的磷酸化。 EGFR抑制剂AG1478减弱ERK(细胞外信号调节的激酶)活化并部分降低细胞存活率。用PDGFR抑制剂AG1296进行的预处理消除了ISO诱导的Akt(也称为蛋白激酶B)磷酸化,并导致细胞活力降低。此外,Src酪氨酸激酶抑制剂PP2阻断了ISO介导的Akt和ERK激活,并严重抑制了生存能力。因此,在原代新生大鼠心肌细胞中,β2-AR抑制剂而不是β1-AR抑制剂消除了EGFR和PDGFR的反式激活,这分别与Akt和ERK的激活有关。结果表明,β2-AR使PDGFR和EGFR活化,从而促进心肌细胞的存活。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号