Flavin-containing monooxygenase, a new clue of pathological proteins in the rotenone model of parkinsonism.
Parkinson's disease (PD) is a major age-related neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra par compacta (SNpc) and accumulation of aggregated alpha-synuclein in brain areas. Rotenone is a neurotoxin that is routinely used to model PD, thus to help us understand the mechanisms of neural death. Flavin-containing monooxygenase (FMO), usually known as an important hepatic microsomal enzyme like cytochrome P450, was found to play a role in the brain recent years. In our study we aimed to find out the role that FMO might play in PD pathology. Thus we successfully generated rotenone model in primary midbrain dopaminergic neurons and identified the apoptosis of neurons caused by rotenone. We found that in rotenone model of Parkinsonism, the expression/protein level of parkin and FMO1 were decreased accompanied by the activation of caspase 3. Blocking FMO activity by FMO inhibitor methimazole directly caused activation of caspase 3, meanwhile parkin protein level was decreased. Our data indicated that FMO, whose dysfunction could be a reason for the apoptosis of dopaminergic neurons in rotenone model, might be a new clue of pathological proteins in rotenone model of parkinsonism. Meanwhile, it was suggested that parkin function was compromised in neuro-pathological states, thereby further adding to the cellular survival stress.
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Boyu
B
Li
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yuhe
Y
Yuan
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Wanqing
W
Zhang
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Wenbin
W
He
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jinfeng
J
Hu
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: chennh@imm.ac.cn.
Naihong
N
Chen
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D008713:Methimazole / Q000494:pharmacology; D010105:Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017207:Rats, Sprague-Dawley; D012402:Rotenone; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D012402:Rotenone; D008713:Methimazole; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D053148:Caspase 3
Apoptosis; Flavin-containing monooxygenase; Parkin; Parkinson's disease; Rotenone