Coenzyme Q10 reduces the toxicity of rotenone in neuronal cultures by preserving the mitochondrial membrane potential

Defects in mitochondrial energy metabolism due to respiratory chain disorders lead to a decrease in mitochondrial membrane potential (ΔΨm) and induce apoptosis. Since coenzyme Q10 (CoQ10) plays a dual role as an antioxidant and bioenergetic agent in the respiratory chain, it has attracted increasing attention concerning the prevention of apoptosis in mitochondrial diseases. In this study the potential of CoQ10 to antagonize the apoptosis‐inducing effects of the respiratory chain inhibitor rotenone was explored by video‐enhanced microscopy in SH‐SY5Y neuroblastoma cells. The cationic fluorescent dye JC‐1 which exhibits potential‐dependent accumulation in mitochondria was used as an indicator to monitor changes in ΔΨm. The relative changes in fluorescence intensity after incubation with rotenone for 15 minutes were calculated. Pre‐treatment with CoQ10 (10 or 100 μM) for 48h led to a significant reduction of rotenone‐induced loss of ΔΨm. These results suggest, that cytoprotection by CoQ10 may be mediated by raising cellular resistance against the initiating steps of apoptosis, namely the decrease of ΔΨm. Whether these data may provide new directions for the development of neuroprotective strategies has to be investigated in future studies.

[1]  J. Turrens,et al.  Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria. , 1980, The Biochemical journal.

[2]  K. Soliman,et al.  Subject Index, Vol. 39, 1989 , 1989 .

[3]  S Yorifuji,et al.  Long‐term coenzyme Q10 therapy for a mitochondrial encephalomyopathy with cytochrome c oxidase deficiency , 1989, Neurology.

[4]  N. Bresolin,et al.  Ubidecarenone in the treatment of mitochondrial myopathies: a multi-center double-blind trial , 1990, Journal of the Neurological Sciences.

[5]  T. Smith,et al.  J-aggregate formation of a carbocyanine as a quantitative fluorescent indicator of membrane potential. , 1991, Biochemistry.

[6]  N. Nishitani,et al.  Marked reduction in CSF lactate and pyruvate levels after CoQ therapy in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke‐like episodes (MELAS) , 1991, Acta neurologica Scandinavica.

[7]  P. Matthews,et al.  Coenzyme Q10 with multiple vitamins is generally ineffective in treatment of mitochondrial disease , 1993, Neurology.

[8]  C. Franceschi,et al.  A new method for the cytofluorimetric analysis of mitochondrial membrane potential using the J-aggregate forming lipophilic cation 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolcarbocyanine iodide (JC-1). , 1993, Biochemical and biophysical research communications.

[9]  G. Dallner,et al.  Biochemical, physiological and medical aspects of ubiquinone function. , 1995, Biochimica et biophysica acta.

[10]  L. Landi,et al.  The role of DT-diaphorase in the maintenance of the reduced antioxidant form of coenzyme Q in membrane systems. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[11]  P. Navas,et al.  Role of cytochrome b5 reductase on the antioxidant function of coenzyme Q in the plasma membrane. , 1997, Molecular aspects of medicine.

[12]  J C Reed,et al.  Mitochondria and apoptosis. , 1998, Science.

[13]  J. Höper,et al.  Electronic light microscopy combined with spectrophotometry allows real-time analysis of structures at the subcellular level , 1998, Physiological measurement.

[14]  K. Abe,et al.  Effect of coenzyme Q10 in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS): Evaluation by noninvasive tissue oximetry , 1999, Journal of the Neurological Sciences.

[15]  H. Krinke,et al.  Effects of heat shock on the functional morphology of cell organelles observed by video‐enhanced microscopy , 1999, The Anatomical record.

[16]  D. Wallace Mitochondrial diseases in man and mouse. , 1999, Science.

[17]  W. Tatton,et al.  Apoptosis in neurodegenerative diseases: the role of mitochondria. , 1999, Biochimica et biophysica acta.

[18]  A. Munnich,et al.  Quinone-responsive multiple respiratory-chain dysfunction due to widespread coenzyme Q10 deficiency , 2000, The Lancet.

[19]  E. Mayatepek,et al.  Coenzyme Q10 in plasma and erythrocytes: comparison of antioxidant levels in healthy probands after oral supplementation and in patients suffering from sickle cell anemia. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[20]  P. O'Brien,et al.  Coenzyme Q Cytoprotective Mechanisms for Mitochondrial Complex I Cytopathies Involves NAD(P)H: Quinone Oxidoreductase 1(NQO1) , 2002, Free radical research.

[21]  J. Salonen,et al.  Coenzyme Q10: Absorption, Antioxidative Properties, Determinants, and Plasma Levels , 2002, Free radical research.

[22]  M. Beal,et al.  Coenzyme Q10 as a possible treatment for neurodegenerative diseases. , 2002, Free radical research.

[23]  S. Dimauro,et al.  Coenzyme Q– responsive Leigh's encephalopathy in two sisters , 2002, Annals of neurology.

[24]  G. Fiskum,et al.  Mitochondrial Mechanisms of Neural Cell Death and Neuroprotective Interventions in Parkinson's Disease , 2003, Annals of the New York Academy of Sciences.

[25]  F. L. Crane,et al.  The essential functions of coenzyme Q , 2004, The clinical investigator.