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First published online 13 February 2007
doi: 10.1242/jcs.03393

Journal of Cell Science 120, 895-907 (2007)
Published by The Company of Biologists 2007
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Research Article

Survivin mediates the anti-apoptotic effect of {delta}-opioid receptor stimulation in cardiomyocytes

Ling-Ling Yao1,*, Yong-Gang Wang2,*, Wen-Jie Cai1, Tai Yao1 and Yi-Chun Zhu1,{ddagger}

1 Department of Physiology and Pathophysiology, Fudan University Shanghai Medical College, 138 Yi Xue Yuan Road, Shanghai 200032, China
2 Department of Neurobiology, Second Military Medical University, Shanghai 200433, China

{ddagger} Author for correspondence (e-mail: yczhu{at}shmu.edu.cn)

Accepted 5 January 2007

Survivin is known to be essential for cell division and to inhibit apoptosis during embryonic development and in adult cancerous tissues. However, the cardiovascular role of survivin is unknown. We observed that in cardiomyocytes cultured under conditions of serum and glucose deprivation (DEPV), the levels of survivin, Bcl-2 and extracellular signal-regulated kinase (ERK) were positively correlated with the anti-apoptotic action of a {delta}-opioid receptor agonist, [D-Ala2, D-Leu5]-enkephalin acetate (DADLE). By contrast, Bax translocation, mitochondrial membrane damage and reactive oxygen species (ROS) production were inversely correlated with the changes of survivin and Bcl-2. The use of RNA interference (RNAi) targeting survivin increased DEPV-induced cardiomyocyte apoptosis, whereas the anti-apoptotic effect of DADLE was blunted by survivin RNAi. Moreover, survivin transfection and overexpression provided protection against DEPV-induced cardiomyocyte apoptosis. Inhibition of ERK prevented the DADLE-induced decrease in apoptosis and Bax translocation, and increase in survivin and Bcl-2. DADLE-induced increase in survivin was also blunted by phosphoinositol 3-kinase (PI 3-kinase) inhibition. In conclusion, the present study provides the first direct evidence of an anti-apoptotic role of survivin mediating the anti-apoptotic effect of {delta}-opioid receptor activation in cardiomyocytes. ERK and PI 3-kinase were found to be upstream regulators of survivin. Mitochondrial membranes as well as ROS, Bcl-2 and Bax were also involved in this anti-apoptotic action.

Key words: Survivin, Apoptosis, {delta}-opioid receptor, DADLE, Cardiomyocyte


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© The Company of Biologists Ltd 2007