Adiponectin Attenuates Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury Through Inhibition of Endoplasmic Reticulum Stress

作者：Bian, Yun-fei; Hao, Xiao-yan; Gao, Feng; Yang, Hui-yu; Zang, Nana; Xiao, Chuan-shi^*

来源：Journal of Investigative Medicine, 2011, 59(6): 921-925.

• adiponectin
• hypoxia-reoxygenation
• endoplasmic reticulum stress
• p38 MAPK
• cell death

Adiponectin (APN) is a potent cardioprotective molecule. The present study aims to investigate the underlying mechanism(s) for its cardioprotective effect. We isolated primary cardiomyocytes from neonatal rats and established an in vitro model of hypoxia/reoxygenation (H/R). The cardiomyocytes were randomly divided into 6 groups: saline group (control), dithiothreitol group (5 mM dithiothreitol for 2 hours), H/R group, H/R + APN group (incubation with 30 mu g/mL APN, followed by H/R), H/R + APN + SB203580 (SB) group (treatment with 30 mu g/mL APN and 5 KM SB, followed by H/R), and H/R + SB group (exposure to 5 KM SB and then H/R). Cell death was detected by measuring lactate dehydrogenase release. The expression levels of hypoxia-inducible factor 1 alpha and endoplasmic reticulum stress-related genes including GRP78, caspase-12, C/EBP homologous protein, and p38 mitogen-activated protein kinase were examined. Cardiomyocytes exposed to H/R showed a significant increase in lactate dehydrogenase leakage and hypoxia-inducible factor 1 alpha protein levels compared with the control cells (P < 0.05). The H/R-provoked cell death was profoundly attenuated by the pretreatment with APN alone, SB alone, or both, which was coupled with decreased expression of GRP78, caspase-12, C/EBP homologous protein, and p38 mitogen-activated protein kinase. These results provide new insights into the mechanism of APN-mediated cardioprotection, which may be partially due to inhibition of endoplasmic reticulum stress response.

• 出版日期2011-8
• 单位山西医科大学第二医院; 山西医科大学