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Ciclopirox protects mitochondria from hydrogen peroxide toxicity.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lee, Sun Jong Jin, Youngnam N. Yoon, Hye Young Choi, Byung-Ok Kim, Hyoung Chun Kim, Hee-Sun Kim, Won-Ki |
| Copyright Year | 2005 |
| Abstract | 1 The mitochondrial respiratory chain produces reactive oxygen species (ROS) during normal electron transport. Despite producing ROS, mitochondria are vulnerable to oxidative stress. Mitochondrial dysfunction has been associated with many degenerative diseases, making it important to identify compounds that protect mitochondria from ROS-mediated toxicity. Here we report that ciclopirox (CPX) blocks H2O2-induced mitochondrial injury by maintaining mitochondrial transmembrane potential (Deltapsim). 2 CPX completely blocked H2O2-stimulated release of lactate dehydrogenase (a marker of cell death) and decrease in MTT reduction (a marker of mitochondrial function) in adenocarcinoma SK-HEP-1 cells. 3 H2O2 rapidly depolarized the Deltapsim, and CPX blocked this H2O2-stimulated Deltapsim decrease. Similar data were obtained in experiments using mitochondria isolated from rat liver. 4 Furthermore, CPX effectively inhibited H2O2-induced mitochondrial permeability transition pore (MPTP) opening. In de-energized mitochondria, however, CPX did not inhibit Ca2+-evoked MPTP opening, indicating that CPX is not a direct inhibitor of the MPTP. 5 Oxygen consumption studies showed that in the presence of pyruvate and malate CPX restored the rate of state 3 to state 4 respiration decreased by H2O2. Consistent with this, CPX replenished ATP levels lowered by H2O2. 6 The present results indicate that CPX protects SK-HEP-1 cells from H2O2 cytotoxicity by inhibiting Deltapsim decrease and indirectly preventing MPTP opening. |
| Starting Page | 973 |
| Ending Page | 978 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://ilsongls.hallym.ac.kr/hwp/second_13.pdf |
| PubMed reference number | 15806112v1 |
| Volume Number | 145 |
| Issue Number | 4 |
| Journal | British journal of pharmacology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Abnormal degeneration Adenocarcinoma Adenosine Triphosphate Adverse reaction to drug Cell Death Cessation of life Hydrogen Peroxide Inhibition Lactate Dehydrogenase Lactic acid MPTP Poisoning Membrane Potential, Mitochondrial Mitochondrial electron transport chain Neurodegenerative Disorders Oxidative Stress Peroxides Pyruvates Reactive Oxygen Species ciclopirox malate mitochondrial permeability transition pore monooxyethylene trimethylolpropane tristearate |
| Content Type | Text |
| Resource Type | Article |
