β3-adrenoceptor impacts apoptosis in cultured cardiomyocytes via activation of PI3K/Akt and p38MAPK
β3-adrenoceptor impacts apoptosis in cultured cardiomyocytes via activation of PI3K/Akt and p38MAPK
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DOI：
10.1007/s11596-016-1533-7
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发表时间：
2016-02
期刊：
影响因子：
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通讯作者：
M. Ma;Xiao-li Zhu;Li Wang;Xiao-fang Hu;Zhong Wang;Jin Zhao;Yi-Tong Ma;Yining Yang;Bang-dang Chen;Fen Liu
中科院分区：
文献类型：
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作者：
M. Ma;Xiao-li Zhu;Li Wang;Xiao-fang Hu;Zhong Wang;Jin Zhao;Yi-Tong Ma;Yining Yang;Bang-dang Chen;Fen Liu
β3-肾上腺素受体（β3-AR）可促进心肌细胞凋亡。然而，这种受体在人类心肌中的确切生理作用和重要性及其潜在的作用模式尚未完全阐明。本研究旨在探讨β3-AR对心肌细胞凋亡的促进作用及对去甲肾上腺素（NE）损伤的影响。采用TUNEL法和Annexin V/propidium iodide凋亡检测法分析NE诱导的心肌细胞凋亡。此外，我们还研究了NE诱导的凋亡标志基因Akt和p38 MAPK、其磷酸化对应物p-Akt和p-p38 MAPK、caspase-3、Bcl-2和Bax的锡永。此外，我们确定了用β3-AR激动剂和拮抗剂处理48小时对这些标记基因表达的影响。β3-AR过表达可增加CM凋亡，并伴有caspase-3、bax/bcl-2和p-p38 MAPK表达增加。相反，β3受体阻滞剂减少CM的凋亡和相关的Akt表达升高。我们通过PI 3 K/Akt通路和p38 MAPK介导的促凋亡通路确定了一种新的有效的抗凋亡机制。
β3-adrenoceptor (β3-AR) has been shown to promote myocardial apoptosis. However, the exact physiological role and importance of this receptor in the human myocardium, and its underlying mode of action, have not been fully elucidated. The present study aimed to determine the effects of β3-AR on the promotion of myocardial apoptosis and on norepinephrine (NE) injury. We analyzed NE-induced cardiomyocyte (CM) apoptosis by using a TUNEL and an annexin V/propidium iodide apoptosis aβsay. Furthermore, we investigated the NE-induced expreβsion of the apoptosis marker genes Akt and p38MAPK, their phosphorylated counterparts p-Akt and p-p38MAPK, caspase-3, Bcl-2, and Bax. In addition, we determined the effect of a 48-h treatment with a β3-AR agonist and antagonist on expression of these marker genes. β3-AR overexpression was found to increase CM apoptosis, accompanied by an increased expression of caspase-3, bax/bcl-2, and p-p38MAPK. In contrast, the β3-blocker reduced apoptosis of CMs and the associated elevated Akt expression. We identified a novel and potent anti-apoptosis mechanism via the PI3K/Akt pathway and a pro-apoptosis pathway mediated by p38MAPK.