Advanced glycation end‐products impair Na+/K+‐ATPase activity in diabetic cardiomyopathy: Role of the adenosine monophosphate‐activated protein kinase/sirtuin 1 pathway. (February 2014)

• Record Type: Journal Article
• Authors: Yuan, Qiong; Zhou, Qian‐Yi; Liu, Du; Yu, Lun; Zhan, Lin; Li, Xiao‐Jing; Peng, Hong‐Yan; Zhang, Xiu‐Ling; Yuan, Xin‐Chu
• Is Part Of: Clinical and experimental pharmacology and physiology. Volume 41:Number 2(2014:Feb.)
• Page Start: 127
• Page End: 133
• Publication Date: 2014-02
• Subjects: Clinical pharmacology -- Periodicals; Pharmacology, Experimental -- Periodicals; Physiology, Experimental -- Periodicals; Physiology, Pathological -- Periodicals; 615.1
• DOI: 10.1111/1440-1681.12194
• Languages: English
• ISSNs: 0305-1870

Abstract

<abstract abstract-type="main" id="cep12194-abs-0001"> <title>Summary</title> <p> <list id="cep12194-list-0001" list-type="order"> <list-item> <p>Decreased Na<sup>+</sup>/K<sup>+</sup>‐ATPase activity, and both sirtuin 1 (SIRT1) and adenosine monophosphate‐activated protein kinase (AMPK) have been reported to be involved in the development of diabetic cardiomyopathy (DCM).</p> </list-item> <list-item> <p>The present study aimed to investigate the advanced glycation end‐products (AGE) that impair Na<sup>+</sup>/K<sup>+</sup>‐ATPase stability by regulating the AMPK/SIRT1 pathway during progression of DCM.</p> </list-item> <list-item> <p>To study type 1 diabetic mellitus (T1DM), a disease model in rats was established by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg), and neonatal rat cardiomyocytes were also cultured. Heart function was detected by Doppler, and SIRT1 and AMPK protein expression were detected by immunohistochemistry and western blotting. Na<sup>+</sup>/K<sup>+</sup>‐ATPase activity was also monitored.</p> </list-item> <list-item> <p>Using <italic>in vivo</italic> rat models of DCM, we showed that Na<sup>+</sup>/K<sup>+</sup>‐ATPase activity decreased when both AMPK and SIRT1 expression were downregulated. <italic>In vitro</italic>, AGE impaired Na<sup>+</sup>/K<sup>+</sup>‐ATPase activity and decreased the AMPK and SIRT1 expression.</p> </list-item> <list-item> <p>Sirtuin 1 overexpression increased Na<sup>+</sup>/K<sup>+</sup>‐ATPase activity. 5‐aminoimidazole‐4‐carboxamide‐3‐ribonucleoside (AICAR) upregulated SIRT1 expression and increased Na<sup>+</sup>/K<sup>+</sup>‐ATPase activity, which could be partially abolished by splitomicin.</p> </list-item> <list-item> <p>Our results suggest that the dysfunction of DCM is related to AGE‐induced Na<sup>+</sup>/K<sup>+</sup>‐ATPase activity impairment through a mechanism involving the AMPK/SIRT1 pathway.</p> </list-item> </list> </p> </abstract>