title: β3-adrenoceptor impacts apoptosis in cultured cardiomyocytes via activation of PI3K/Akt and p38MAPK.
abstract: 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 assay. Furthermore, we investigated the NE-induced expression 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.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China.
authors.forename: Miao-Miao
authors.initials: MM
authors.lastname: Ma
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China.
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Zhu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China. mcmwl@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China.
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Hu
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Medicine, Shihezi University, Shihezi, 832008, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Heart Centre, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
authors.forename: Yi-Tong
authors.initials: YT
authors.lastname: Ma
authors.affiliation: Heart Centre, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Yang
authors.affiliation: Heart Centre, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
authors.forename: Bang-Dang
authors.initials: BD
authors.lastname: Chen
authors.affiliation: Heart Centre, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022702:Receptors, Adrenergic, beta-3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D022702:Receptors, Adrenergic, beta-3; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Akt; apoptosis; cardiomyocytes; norepinephrine; p38MAPK; β3-adrenoreceptor
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