Menadione reduces rotenone-induced cell death in cerebellar granule neurons.
Oxidative stress has been implicated in neuronal death caused by cerebral ischemia or some neurologic disorders. Chemical hypoxia (term defining the simulation by using respiratory inhibitors) chosen as in vitro ischemic model, was induced in primary cultures of rat cerebellar granule neurons by inhibitors of mitochondrial electron transport such as rotenone or paraquat (complex I), 3-nitropropionic acid (3-NPA, complex II), antimycin A (complex III), or sodium azide (complex IV). All compounds caused neuronal death determined by trypan blue staining and MTT-test. On the other hand, neurotoxicity of rotenone and paraquat but not of 3-NPA, antimycin or azide was significantly abolished by menadione (vitamin K3, 2-methyl-1,4-naphthoquinone). This neuroprotective effect of menadione was associated with a decrease of rotenone-induced free radical production.
Isaev
Nickolay K
NK
Department of Bioenergetics, AN Belozersky Institute of Physico-Chemical Biology, Moscow State University, 119992 Moscow, Russia.
Stelmashook
Elena V
EV
Ruscher
Karsten
K
Andreeva
Nadezhda A
NA
Zorov
Dmitry B
DB
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000037:antagonists & inhibitors / Q000633:toxicity*; D024483:Vitamin K 3 / Q000494:pharmacology*
D012402:Rotenone; D024483:Vitamin K 3