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, 24 (6), 1211-1217

Heme as a Target for Protection Against Doxorubicin-Induced Apoptosis in H9c2 Cardiomyocytes

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Heme as a Target for Protection Against Doxorubicin-Induced Apoptosis in H9c2 Cardiomyocytes

Na Liu et al. Cell Stress Chaperones.

Abstract

Heme homeostasis is of vital importance to many biological processes associated with cell redox activity. However, the role of heme in the doxorubicin (DOX)-induced cardiotoxicity is still not clear. The aim of the present study was to test the hypothesis that heme is related to the DOX-induced oxidative stress and inhibition of heme expression may protect H9c2 cardiomyocytes against DOX-induced cardiotoxicity. For the evaluation of heme changing under doxorubicin treatment, H9c2 cells were treated with 0.5, 1, 2, and 4 mg/mL doxorubicin respectively. H9c2 cells were divided into 5 groups: Control group (cells were cultured without intervention), DOX group (cells were treated with 2 mg/mL doxorubicin for 6 h), Heme depletion+DOX group (cells were cultured with heme-depleted serum media, 0.5 mM succinylacetone and 2 mg/mL doxorubicin), Heme group (cells were treated with 30 μM heme), and Heme depletion+DOX+Heme group. Apoptotic cells were detected by flow cytometry with Annexin V-FITC/PI. The intracellular oxidant levels were measured by DCFH-DA fluorescence. The levels of heme were detected by ELISA. Doxorubicin significantly increased intracellular heme level from 5013 ± 187 ng/mL to the highest level of 11,720 ± 107 ng/mL, as well as the intracellular oxidants and cell apoptosis rate elevated by the increase of doxorubicin concentration. Heme depletion can significantly suppress the DOX-induced apoptosis from 39.8 ± 0.5% to 20.8 ± 0.5% (p < 0.001). Re-supplemented with exogenous heme partially but significantly restored the DOX-induced apoptosis. Heme plays an important role in doxorubicin toxicity-induced cardiomyocyte injury. By appropriate reduction in the accumulation of free heme in cardiomyocytes, doxorubicin-induced cardiotoxicity may be alleviated.

Keywords: Apoptosis; Cardiomyocytes; Doxorubicin; Heme.

Conflict of interest statement

The authors declare that they have no conflict of interest.

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