Coenzyme Q10 protects SHSY5Y neuronal cells from beta amyloid toxicity and oxygen-glucose deprivation by inhibiting the opening of the mitochondrial permeability transition pore.
Coenzyme Q10 (CoQ10) is an essential biological cofactor which increases brain mitochondrial concentration and exerts neuroprotective effects. In the present study, we exposed SHSY5Y neuroblastoma cells to neurotoxic beta amyloid peptides (Abeta) and oxygen glucose deprivation (OGD) to investigate the neuroprotective effect of 10 microM CoQ10 by measuring (i) cell viability by the MTT assay, (ii) opening of the mitochondrial permeability transition pore via the fluorescence intensity of calcein-AM, and (iii) superoxide anion concentration by hydroethidine. Cell viability (mean +/- S.E.M.) was 55.5 +/- 0.8% in the group exposed to Abeta + OGD, a value lower than that in the Abeta or OGD group alone (P < 0.01). CoQ10 had no neuroprotective effect on cell death induced by either Abeta or OGD, but increased cell survival in the Abeta + OGD group to 57.3 +/- 1.7%, which was higher than in the group treated with vehicle (P < 0.05). The neuroprotective effect of CoQ10 was blocked by administration of 20 microM atractyloside. Pore opening and superoxide anion concentration were increased in the Abeta + OGD group relative to sham control (P < 0.01), and were attenuated to the sham level (P > 0.05) when CoQ10 was administered. Our results demonstrate that CoQ10 protects neuronal cells against Abeta neurotoxicity together with OGD by inhibiting the opening of the pore and reducing the concentration of superoxide anion.
Li
Geng
G
The Jockey Club MRI Centre, The University of Hong Kong, China. ligeng@eee.hku.hk
Zou
Liang-Yu
LY
Cao
Chun-Mei
CM
Yang
Edward S
ES
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D001278:Atractyloside / Q000494:pharmacology; D015687:Cell Hypoxia / Q000502:physiology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003067:Coenzymes; D005452:Fluoresceins; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D045022:Lactate Dehydrogenases / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D000083162:Mitochondrial Permeability Transition Pore; D009447:Neuroblastoma; D009474:Neurons / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D003067:Coenzymes; D005452:Fluoresceins; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013481:Superoxides; D014451:Ubiquinone; C085925:calcein AM; D001278:Atractyloside; D045022:Lactate Dehydrogenases; C024989:coenzyme Q10; D005947:Glucose