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Abstract
HL-1 cardiomyocytes were subjected to simulated hypoxia, in the presence of cobalt chloride, which resulted in reduction of cell viability and induction of DNA laddering, indicating the activation of the apoptotic cascade. In the presence of trolox, ascorbic acid, melatonin and the hybrid compound of trolox and lipoic acid (LaT 3a), cell viability was increased, with LaT 3a exhibiting the best effect. Antioxidant treatment restored ATP levels, abolished laddering of DNA, abrogated MPTP opening, Bax translocation to the mitochondria and cytochrome c release to the cytoplasm. Moreover, severe hypoxia, was found to destabilize hypoxia inducible factor-1α (Hif-1α) mRNA. Reduction of oxidative stress attenuated this effect, implying a possible anti-apoptotic action of the master regulator of hypoxia response. Our data suggest that antioxidants can maintain cell function and survival by inhibiting the mitochondrial apoptotic pathway and stabilizing Hif-1α.
| Abbreviations | ||
| ROS | = | reactive oxygen species |
| LaT | = | lipoic acid-trolox |
| MPTP | = | mitochondrial permeabilization transition pore |
| Hif-1α | = | hypoxia inducible factor-1α |
| ETC | = | electron transport chain |
| VDAC | = | voltage dependent anion channel |
| ANT | = | adenine nucleotide transporter |
| HRE | = | hypoxia response element |
| VHL | = | Von Hippel Lindau |
| VEGF | = | vascular endothelial growth factor |
| ANP | = | atrial natriuretic peptide |
| ANF | = | atrial natriuretic factor |
| GAPDH | = | glyceraldehyde-3-phosphate dehydrogenase |
| αHIF | = | antisense Hif-1α |
| Abbreviations | ||
| ROS | = | reactive oxygen species |
| LaT | = | lipoic acid-trolox |
| MPTP | = | mitochondrial permeabilization transition pore |
| Hif-1α | = | hypoxia inducible factor-1α |
| ETC | = | electron transport chain |
| VDAC | = | voltage dependent anion channel |
| ANT | = | adenine nucleotide transporter |
| HRE | = | hypoxia response element |
| VHL | = | Von Hippel Lindau |
| VEGF | = | vascular endothelial growth factor |
| ANP | = | atrial natriuretic peptide |
| ANF | = | atrial natriuretic factor |
| GAPDH | = | glyceraldehyde-3-phosphate dehydrogenase |
| αHIF | = | antisense Hif-1α |