Myocardial ischemia/reperfusion (IR) injury leads to structural changes in the heart muscle later followed by functional decline due to progressive fibrous replacement. Hence approaches to minimize IR injury are devised, including ischemic pre-and postconditioning. Mild uncoupling of oxidative phosphorylation is one of the mechanisms suggested to be cardioprotective as chemical uncoupling mimics ischemic preconditioning. Uncoupling protein 2 is proposed to be the physiological counterpart of chemical uncouplers and is thought to be a part of the protective machinery of cardiomyocytes. Morphological changes in the mitochondrial network likely accompany the uncoupling with mitochondrial fission dampening the signals leading to cardiomyocyte death. Here we review recent data on the role of uncoupling in cardioprotection and propose that low concentrations of dietary polyphenols may elicit the same cardioprotective effect as dinitrophenol and FCCP, perhaps accounting for the famed "French paradox".
- MeSH
- Cell Death drug effects MeSH
- Dinitrophenols therapeutic use MeSH
- Phenols therapeutic use MeSH
- Flavonoids therapeutic use MeSH
- Ion Channels metabolism MeSH
- Ischemic Preconditioning, Myocardial MeSH
- Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone therapeutic use MeSH
- Myocytes, Cardiac metabolism pathology MeSH
- Cardiotonic Agents therapeutic use MeSH
- Humans MeSH
- Mitochondrial Proteins metabolism MeSH
- Myocardium metabolism pathology MeSH
- Oxidative Phosphorylation MeSH
- Myocardial Reperfusion Injury drug therapy metabolism pathology MeSH
- Uncoupling Agents therapeutic use MeSH
- Signal Transduction drug effects MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Microtubule disruptors, widely known as antimitotics, have broad applications in human medicine, especially as anti-neoplastic agents. They are subject to biotransformation within human body frequently involving cytochromes P450. Therefore antimitotics are potential culprits of drug-drug interactions on the level of activity as well as expression of cytochromes P450. This review discusses the effects of four well-known natural antimitotics: colchicine, taxol (paclitaxel), vincristine, and vinblastine, and a synthetic microtubule disruptor nocodazole on transcriptional activity of glucocorticoid and aryl hydrocarbon receptors. It appears that microtubules disarray restricts the signaling by these two nuclear receptors regardless of cell cycle phase. Consequently, intact microtubules play an important role in the regulation of expression of cytochromes P450, which are under direct or indirect control of the two nuclear receptors.
- MeSH
- Antimitotic Agents pharmacology MeSH
- Biotransformation MeSH
- Colchicine pharmacology MeSH
- Drug Interactions MeSH
- Humans MeSH
- Microtubules drug effects MeSH
- Nocodazole pharmacology MeSH
- Paclitaxel pharmacology MeSH
- Receptors, Aryl Hydrocarbon metabolism MeSH
- Receptors, Glucocorticoid metabolism MeSH
- Signal Transduction MeSH
- Cytochrome P-450 Enzyme System metabolism MeSH
- Vinblastine pharmacology MeSH
- Vincristine pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
