NDRG2: a newly identified mediator of insulin cardioprotection against myocardial ischemia–reperfusion injury
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- 作者：Zhongchan Sun (1) (2)
Guang Tong (3)
Nan Ma (4)
Jianying Li (2)
Xiujuan Li (1)
Shuang Li (1)
Jingyu Zhou (1)
Lize Xiong (5)
Feng Cao (1)
Libo Yao (2)
Haichang Wang (1)
Lan Shen (2) - 关键词：NDRG2 ; Akt ; Heart ; Ischemia/reperfusion injury ; Insulin
- 刊名：Basic Research in Cardiology
- 出版年：2013
- 出版时间：May 2013
- 年：2013
- 卷：108
- 期：3
- 全文大小：1184KB
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Guang Tong (3)
Nan Ma (4)
Jianying Li (2)
Xiujuan Li (1)
Shuang Li (1)
Jingyu Zhou (1)
Lize Xiong (5)
Feng Cao (1)
Libo Yao (2)
Haichang Wang (1)
Lan Shen (2)
1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15# Changle Western Road, Xi’an, 710032, China
2. The State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, 17# Changle Western Road, Xi’an, 710032, China
3. Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China
4. Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China
5. Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China - ISSN：1435-1803
文摘
The N-myc downstream-regulated gene 2 (NDRG2) is involved in cell apoptosis and survival. Although reported to be highly expressed in the cardiac tissue, the biological function of NDRG2 in the heart remains to be established. Insulin exerts protective effects against myocardial ischemia/reperfusion (I/R) injury through the PI3K/Akt pathway. Here, we examined the changes in phosphorylation of NDRG2, a novel substrate and phosphoprotein of Akt, in insulin-induced protection against myocardial I/R. Rat hearts were subjected to 30?min regional ischemia followed by reperfusion with or without insulin at the onset of reperfusion. Reperfusion with insulin inhibited myocardial apoptosis and reduced infarct size, as well as significantly up-regulated myocardial Akt and NDRG2 phosphorylation levels compared with the I/R group. These effects of insulin were blocked by pretreatment with the PI3K inhibitor wortmannin or Akt inhibitor. To further ascertain the role of NDRG2 in insulin-induced cardioprotection, cardiomyocytes were transduced with a lentivirus encoding shRNA targeting NDRG2 (loss-of-function), which rendered the cells more susceptible to I/R injury and significantly blunted the anti-apoptotic effect of insulin. Moreover, the NDRG2 shRNA lentivirus was tested in vivo, and NDRG2 knockdown aggravated myocardial I/R injury and attenuated the insulin-mediated cardioprotection against I/R injury. Taken together, these results suggest a novel role of PI3K/Akt/NDRG2 signaling in the cardioprotective effect of insulin.