Regulation of the cardiac mitochondrial membrane potential by retinoids Journal Article
| Authors: | Koritchneva, I.; Waka, J.; Hammerling, U. |
| Article Title: | Regulation of the cardiac mitochondrial membrane potential by retinoids |
| Abstract: | Cardiomyocytes suffering irreversible damage under oxidative stress during ischemia activate their suicide program. Mitochondria play a key role in this process, while they themselves are subject to regulation by a number of signaling pathways. We demonstrate here that retinoids influence mitochondrial function in cardiomyocytes. Depending on their chemical nature, retinoids can either ameliorate or exacerbate stress-related damage. Thus, vitamin A, retinol, was protective because retinol deprivation enhanced oxidative damage, as indicated by rapid loss of mitochondrial membrane potential. Supplementation with a physiological concentration of retinol reversed this effect. Anhydroretinol (AR), a known antagonist, which works by displacing retinol from the common binding sites on serine/threonine kinases, also caused mitochondrial membrane depolarization. The AR effect was both Ca2+-dependent and cyclosporin-sensitive, suggesting an upstream signaling mechanism rather than direct membrane effect. Our results agree with a model where retinol supports mitochondrial integrity by enabling upstream signaling processes. The consequences of disrupting these processes by AR are opening of the permeability transition pore, release of cytochrome c, and activation of the suicide program. |
| Keywords: | controlled study; unclassified drug; nonhuman; flow cytometry; animal cell; animals; cells, cultured; microscopy, confocal; serine; animal model; blotting, western; regulatory mechanism; rat; newborn; reactive oxygen species; vitamin supplementation; binding site; threonine; rats; hydrogen peroxide; oxidative stress; rats, sprague-dawley; retinol; retinol deficiency; actins; mitochondrial membrane; heart muscle cell; oxidation-reduction; retinoid; myocardium; electrophoresis, polyacrylamide gel; retinoids; calcium ion; membrane potentials; anhydroretinol; ionophores; membrane depolarization; membrane potential; retinol derivative; mitochondria, heart; priority journal; article; heart mitochondrion; carbonyl cyanide p-trifluoromethoxyphenylhydrazone; mitochondrial swelling |
| Journal Title: | Journal of Pharmacology and Experimental Therapeutics |
| Volume: | 305 |
| Issue: | 2 |
| ISSN: | 0022-3565 |
| Publisher: | American Society for Pharmacology and Experimental Therapeutics |
| Date Published: | 2003-05-01 |
| Start Page: | 426 |
| End Page: | 433 |
| Language: | English |
| DOI: | 10.1124/jpet.103.048900 |
| PUBMED: | 12606625 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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