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β3-adrenoceptor impacts apoptosis in cultured cardiomyocytes via activation of PI3K/Akt and p38MAPK

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Summary

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.

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Authors and Affiliations

  1. Department of Cardiology, the First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi, 832008, China

    Miao-miao Ma  (马苗苗), Xiao-li Zhu  (朱晓丽), Li Wang  (王 丽), Xiao-fang Hu  (胡小芳) & Zhong Wang  (王 忠)

  2. Department of Pathology, School of Medicine, Shihezi University, Shihezi, 832008, China

    Jin Zhao  (赵 瑾)

  3. Heart Centre, the First Affiliated Hospital of Xinjiang Medical University, Urumqi, 830054, China

    Yi-tong Ma  (马依彤), Yi-ning Yang  (杨毅宁), Bang-dang Chen  (陈邦党) & Fen Liu  (刘 芬)

Authors
  1. Miao-miao Ma  (马苗苗)
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  2. Xiao-li Zhu  (朱晓丽)
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  3. Li Wang  (王 丽)
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  4. Xiao-fang Hu  (胡小芳)
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  5. Zhong Wang  (王 忠)
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  6. Jin Zhao  (赵 瑾)
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  7. Yi-tong Ma  (马依彤)
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  8. Yi-ning Yang  (杨毅宁)
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  9. Bang-dang Chen  (陈邦党)
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  10. Fen Liu  (刘 芬)
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Corresponding author

Correspondence to Li Wang  (王 丽).

Additional information

This project was supported by the National Natural Science Foundation of China (No. 81260028).

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Ma, Mm., Zhu, Xl., Wang, L. et al. β3-adrenoceptor impacts apoptosis in cultured cardiomyocytes via activation of PI3K/Akt and p38MAPK. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 1–7 (2016). https://doi.org/10.1007/s11596-016-1533-7

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  • DOI: https://doi.org/10.1007/s11596-016-1533-7

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