Alpha1 catalytic subunit of AMPK modulates contractile function of cardiomyocytes through phosphorylation of troponin I

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• 作者：Si Chen^a ; ¹ ; Ping Zhu^b ; ¹ ; Hui-Ming Guo^b ; Raquel Sancho Solis^c ; Yanqing Wang^a ; Yina Ma^a ; Jinli Wang^a ; Junjie Gao^a ; Ji-Mei Chen^b ; Ying Ge^c ; Jian Zhuang^b ; ^{zhuangjianzggd@yahoo.cn" class="auth_mail} ; Ji Li^a ; ^{jli23@buffalo.edu" class="auth_mail}
• 关键词：Contractile function ; AMPK ; Troponin I
• 刊名：Life Sciences
• 出版年：11 March, 2014
• 年：2014
• 卷：98
• 期：2
• 页码：75-82
• 全文大小：1002 K

文摘

Aims

The specific role of AMPK伪1 or AMPK伪2 in mediating cardiomyocyte contractile function remains elusive. The present study investigated how AMPK activation modulates the contractility of isolated cardiomyocytes.

Main methods

Mechanical properties and intracellular Ca^2 + properties were measured in isolated cardiomyocytes. The stress signaling was evaluated using western blot and immunoprecipitation analysis.

Key findings

AMPK activator, A-769662 induced maximal velocity of shortening (+ dL/dt) and relengthening (鈭?#xA0;dL/dt), peak height and peak shortening (PS) amplitude in both WT and AMPK伪2 KO cardiomyocytes, but did not affect time-to-90% relengthening (TR90). AMPK KD cardiomyocytes demonstrated contractile dysfunction compared with cardiomyocytes from WT and AMPK伪2 KO hearts. However, the rise of intracellular Ca^2 + levels as well as intracellular ATP levels has no significant difference among WT, AMPK伪2 KO and AMPK KD groups with and without the presence of A-769662. Besides, WT, AMPK伪2 KO and AMPK KD group displayed a phosphorylated AMPK and downstream acetyl-CoA carboxylase (ACC) phosphorylation. Interestingly, A-769662 also triggered troponin I (cTnI) phosphorylation at Ser¹⁴⁹ site which is related to contractility of cardiomyocytes. Furthermore, the immunoprecipitation analysis revealed that AMPK伪1 of cardiomyocytes was phosphorylated by A-769662.

Significance

This is the first study illustrating that activation of AMPK plays a significant role in mediating the contractile function of cardiomyocytes using transgenic animal models. AMPK activator facilitates the contractility of cardiomyocytes via activating AMPK伪1 catalytic subunit. The phosphorylation of cTnI by AMPK could be a factor attributing to the regulation of contractility of cardiomyocytes.