Water-soluble formulation of Coenzyme Q10 inhibits Bax-induced destabilization of mitochondria in mammalian cells.
Oxidative stress leads to mitochondrial dysfunction, which triggers the opening of the permeability transition pores (PTP) and the release of pro-apoptotic factors causing apoptotic cell death. In a limited number of cell systems, anti-oxidants and free-radical scavengers have been shown to block this response. We have previously reported that coenzyme Q(10) (CoQ(10)), an electron carrier in the mitochondrial respiratory chain, is involved in the reactive oxygen species (ROS) removal and prevention of oxidative stress-induced apoptosis in neuronal cells. However, the mechanism of this protection has not been fully elucidated. In the present study we investigated the effects of CoQ(10) on the mitochondrial events characteristic to apoptosis, especially on the function of pro-apoptotic protein Bax. Our results demonstrated that following a brief exposure of two human cell lines (fibroblasts and HEK293 cells) to H(2)O(2) the intracellular levels of ROS and the association of Bax with the mitochondria significantly increased and the cells underwent apoptosis. Both of these events, as well as the release of cytochrome c from the mitochondria, were blocked by a 24 h pre-treatment with CoQ(10). It is therefore believed that CoQ(10) prevented the collapse of the mitochondrial membrane potential in response to the H(2)O(2) treatment. Recombinant Bax protein alone caused the ROS generation and release of cytochrome c from isolated mitochondria and, again, CoQ(10) inhibited these Bax-induced mitochondrial dysfunctions.
Naderi
Jafar
J
Department of Chemistry and Biochemistry, University of Windsor, Windsor, Ontario, Canada.
Somayajulu-Nitu
Mallika
M
Mukerji
Amit
A
Sharda
Priya
P
Sikorska
Marianna
M
Borowy-Borowski
Henryk
H
Antonsson
Bruno
B
Pandey
Siyaram
S
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D003067:Coenzymes; D045304:Cytochromes c / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012995:Solubility; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014867:Water; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors*
D003067:Coenzymes; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D014867:Water; D014451:Ubiquinone; D045304:Cytochromes c; C024989:coenzyme Q10