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Related Subjects: Biomarkers and Laboratory Testing for Cardiovascular Disease
e0674 Insulin induces phosphorylation of Ndrg2 through activation of Akt in cardiomyocytes during transient ischaemia/reperfusion
  1. Zhongchan Sun,
  2. Feng Cao,
  3. Guang Tong,
  4. Dongdong Sun,
  5. Haichang Wang
  1. Department of Cardiovascular Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China

Abstract

Aims The protein kinase Akt mediates an important cell-survival signalling of insulin through inhibition of apoptosis post cardiac ischaemia/reperfusion (I/R) injury. As Ndrg2 (N-Myc downstream-regulated gene 2) protein is one of Akt-mediated phosphorylation target in C2C12 skeletal muscle cell line, we evaluated whether insulin treatment could lead to Ndrg2 phosphorylation through Akt activation in rat cardiac tissue or cultured primary cardiomyocytes.

Methods Male Sprague-Dawley rats underwent 30 min of ligation of the left anterior descending coronary artery, followed by reperfusion for various periods. Western blot was applied to detect total and phosphorylated Akt and Ndrg2.

Results Our data showed that both Akt and Ndrg2 phosphorylation were increased by 30 min of ischaemia alone compared to those of control group, then they were gradually reduced by following reperfusion, reaching their respective lowest levels after 3 h of reperfusion. In addition, insulin treatment resulted in significant enhancement of phosphorylated Ndrg2 and Akt after 3 h of reperfusion. In vitro, insulin increased Ndrg2 phosphorylation in cardiomyocytes in a wortmannin- and 1L-6-hydroxymethyl-chiro-inositol-2(R)-2-O-methyl-3-O-octa-decyl-carbonate (HIMO)- inhibitable manner, whereas cavtratin, a selective eNOS inhibitor, had no such effect, supporting a likely direct role for Akt.

Conclusions we first demonstrated in rat cardiomyocytes that Ndrg2 phosphorylation level was modulated during transient I/R injury and could be enhanced by activation of Akt secondary to insulin treatment.

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