Biochemical and Biophysical Research Communications, Vol.457, No.4, 602-607, 2015
Adipocytokine, omentin inhibits doxorubicin-induced H9c2 cardiomyoblasts apoptosis through the inhibition of mitochondrial reactive oxygen species
Omentin is a relatively novel adipocyte-derived cytokine mainly expressed in visceral adipose tissues. Blood omentin level decreases in the patients with obesity, hypertension, type 2 diabetes and atherosclerosis. We have previously demonstrated that omentin inhibits key pathological processes for hypertension development, including vascular inflammatory responses, contractile reactivity and structural remodeling. In addition, there are several reports demonstrating that omentin prevents cardiac hypertrophy and myocardial ischemic injury. Doxorubicin (DOX) is an effective anti-cancer drug with cardiotoxic side effect. Here we tested the hypothesis that omentin may prevent DOX-induced cardiac H9c2 rat cardiomyoblasts were treated with DOX in the absence or presence of omentin. Omentin (300 ng/ml, 3 h pretreatment) significantly inhibited DOX (1 mu M, 18 h)-induced decreases in living cell number as determined by a colorimetric cell counting assay. Omentin (300 ng/ml, 3 h) significantly inhibited DOX (1 mu M, 12 h)-induced cleaved caspase-3 expression as determined by Western blotting. Omentin (300 ng/ml, 3 h) significantly inhibited DOX (1 mu M, 6 h)-induced mitochondrial reactive oxygen species (ROS) production as determined by a MitoSOX Red fluorescent staining. In addition, a mitochondrial respiratory chain complex I inhibitor, rotenone (0.5 mu M, 3 h pretreatment), significantly inhibited DOX (1 mu M, 6-18 h)-induced decreases of living cell number, cleaved caspase-3 expression and mitochondrial ROS production. In summary, we for the first time demonstrate that omentin prevents DOX-induced H9c2 cells apoptosis through the inhibition of mitochondria] ROS production. These results indicate omentin as an attractive pharmaco-therapeautic target against DOX-induced cardiac side effect. (C) 2015 Elsevier Inc. All rights reserved.