| First Author | Teixeira G | Year | 2013 |
| Journal | J Mol Cell Cardiol | Volume | 56 |
| Pages | 55-62 | PubMed ID | 23238221 |
| Mgi Jnum | J:213261 | Mgi Id | MGI:5583952 |
| Doi | 10.1016/j.yjmcc.2012.11.023 | Citation | Teixeira G, et al. (2013) Synergistic protective effect of cyclosporin A and rotenone against hypoxia-reoxygenation in cardiomyocytes. J Mol Cell Cardiol 56:55-62 |
| abstractText | Reperfusion of the heart after an ischemic event leads to the opening of a nonspecific pore in the inner mitochondrial membrane, the mitochondrial permeability transition pore (mPTP). Inhibition of mPTP opening is an effective strategy to prevent cardiomyocyte death. The matrix protein cyclophilin-D (CypD) is the best-known regulator of mPTP opening. In this study we confirmed that preconditioning and postconditioning with CypD inhibitor cyclosporin-A (CsA) reduced cell death after hypoxia-reoxygenation (H/R) in wild-type (WT) cardiomyocytes and HL-1 mouse cardiac cell line as measured by nuclear staining with propidium iodide. The complex I inhibitor rotenone (Rot), alone, had no effect on HL-1 and WT cardiomyocyte death after H/R, but enhanced the native protection of CypD-knocked-out (CypD KO) cardiomyocytes. Reduction of cell death was associated with a delay of mPTP opening challenged by H/R and observed by the calcein loading CoCl(2)-quenching technique. Simultaneous inhibition of complex I and CypD increased in a synergistic manner the calcium retention capacity in permeabilized cardiomyocytes and cardiac mitochondria. These results demonstrated that protection by complex I inhibition was CypD dependent. |
