Coenzyme Q10 Prevents Apoptosis by Inhibiting Mitochondrial Depolarization Independently of Its Free Radical Scavenging Property
| Autor: | Andrea Lapucci, Laura Papucci, Sergio Capaccioli, Rosario Brancato, Sandra Zecchi-Orlandini, G.E. Orlandini, Martino Donnini, Lucia Formigli, Alessio Tempestini, G. Carella, Ewa Witort, Nicola Schiavone |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Keratinocytes
Programmed cell death Time Factors Cell Survival Ubiquinone Ultraviolet Rays Blotting Western Coenzymes Respiratory chain Antimycin A Apoptosis DNA Fragmentation Ceramides Biochemistry Mitochondrial apoptosis-induced channel Culture Media Serum-Free Membrane Potentials chemistry.chemical_compound Adenosine Triphosphate Animals Molecular Biology biology Superoxide Dismutase Cytochrome c Respiratory chain complex DNA Free Radical Scavengers Cell Biology Free radical scavenger Caspase 9 Mitochondria Cell biology Microscopy Fluorescence Models Chemical chemistry Caspases biology.protein Rabbits Reactive Oxygen Species Oxidation-Reduction DNA Damage |
| Zdroj: | Journal of Biological Chemistry. 278:28220-28228 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m302297200 |
| Popis: | The permeability transition pore (PTP) is a mitochondrial channel whose opening causes the mitochondrial membrane potential (deltapsi) collapse that leads to apoptosis. Some ubiquinone analogues have been demonstrated previously to modulate the PTP open-closed transition in isolated mitochondria and thought to act through a common PTP-binding site rather than through oxidation-reduction reactions. We have demonstrated recently both in vitro and in vivo that the ubiquitous free radical scavenger and respiratory chain coenzyme Q10 (CoQ10) prevents keratocyte apoptosis induced by excimer laser irradiation more efficiently than other antioxidants. On this basis, we hypothesized that the antiapoptotic property of CoQ10 could be independent of its free radical scavenging ability and related to direct inhibition of PTP opening. In this study, we have verified this hypothesis by evaluating the antiapoptotic effects of CoQ10 in response to apoptotic stimuli, serum starvation, antimycin A, and ceramide, which do not generate free radicals, in comparison to control, free radical-generating UVC irradiation. As hypothesized, CoQ10 dramatically reduced apoptotic cell death, attenuated ATP decrease, and hindered DNA fragmentation elicited by all apoptotic stimuli. This was accompanied by inhibition of mitochondrial depolarization, cytochrome c release, and caspase 9 activation. Because these events are consequent to mitochondrial PTP opening, we suggest that the antiapoptotic activity of CoQ10 could be related to its ability to prevent this phenomenon. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|