Cycloheximide and 4-OH-TEMPO suppress chloramphenicol-induced apoptosis in RL-34 cells via the suppression of the formation of megamitochondria
| Autor: | Masaaki Teranishi, Tsuyoshi Soji, Mariusz Ostrowski, Chieko Kurono, Mariusz Karbowski, Takashi Wakabayashi, Michal Wozniak |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
RL-34 cell
Cell Down-Regulation Apoptosis Biology Cycloheximide Mitochondrion DNA laddering Megamitochondria Antioxidants Cell Line Membrane Potentials Cyclic N-Oxides chemistry.chemical_compound medicine Animals Molecular Biology Protein Synthesis Inhibitors Intracellular Membranes Cell Biology Free radical scavenger Mitochondria Rats Cell biology Chloramphenicol medicine.anatomical_structure chemistry Cell culture Spin Labels TEMPO Reactive Oxygen Species Cell Division |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1449:25-40 |
| ISSN: | 0167-4889 |
| DOI: | 10.1016/s0167-4889(98)00167-0 |
| Popis: | Toxic effects of chloramphenicol, an antibiotic inhibitor of mitochondrial protein synthesis, on rat liver derived RL-34 cell line were completely blocked by a combined treatment with substances endowed with direct or indirect antioxidant properties. A stable, nitroxide free radical scavenger, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, and a protein synthesis inhibitor, cycloheximide, suppressed in a similar manner the following manifestations of the chloramphenicol cytotoxicity: (1) Oxidative stress state as evidenced by FACS analysis of cells loaded with carboxy-dichlorodihydrofluorescein diacetate and Mito Tracker CMTH2MRos; (2) megamitochondria formation detected by staining of mitochondria with MitoTracker CMXRos under a laser confocal microscopy and electron microscopy; (3) apoptotic changes of the cell detected by the phase contrast microscopy, DNA laddering analysis and cell cycle analysis. Since increases of ROS generation in chloramphenicol-treated cells were the first sign of the chloramphenicol toxicity, we assume that oxidative stress state is a mediator of above described alternations of RL-34 cells including MG formation. Pretreatment of cells with cycloheximide or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, which is known to be localized into mitochondria, inhibited the megamitochondria formation and succeeding apoptotic changes of the cell. Protective effects of cycloheximide, which enhances the expression of Bcl-2 protein, may further confirm our hypothesis that the megamitochondria formation is a cellular response to an increased ROS generation and raise a possibility that antiapoptotic action of the drug is exerted via the protection of the mitochondria functions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect