Striatal 19S Rpt6 deficit is related to alpha-synuclein accumulation in MPTP-treated mice.
Striatal mitochondrial proteins were investigated using proteomics in the 1-methyl 4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. Four proteins, 19S proteasome ATPase Rpt6 (19S Rpt6), Lectin-related nature killer cell receptor LY 49S, Zinc finger A20 domain containing 1, and the sodium channel-associated protein 1 isoform 2, were significantly decreased while alpha-synuclein was increased in MPTP-treated mice. The altered levels of 19S Rpt6 and alpha-synuclein were further verified by Western blot. Experiments using small interfering RNA (siRNA) showed that alpha-synuclein was increased by 50% in cultured striatal neurons when 19S Rpt6 was knocked down. Taken together, our results imply that a deficiency in 19S Rpt6 may be partially related to the MPTP-induced increase in alpha-synuclein in the striatum.
Liu
Bin
B
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 1# Xiannongtan Street, Xuanwu District, Beijing 100050, China.
Shi
Qiaoqiao
Q
Ma
Shiping
S
Feng
Nan
N
Li
Jiang
J
Wang
Ling
L
Wang
Xiaoliang
X
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D037181:Lectins, C-Type / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics; D034622:RNA Interference; D055630:Receptors, NK Cell Lectin-Like; D051844:alpha-Synuclein / Q000378:metabolism*
D000950:Antigens, Ly; D037181:Lectins, C-Type; D009498:Neurotoxins; D055630:Receptors, NK Cell Lectin-Like; D051844:alpha-Synuclein; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000251:Adenosine Triphosphatases