Mitochondrial dysfunction, oxidative stress, and apoptosis revealed by proteomic and transcriptomic analyses of the striata in two mouse models of Parkinson's disease.
The molecular mechanisms underlying the changes in the nigrostriatal pathway in Parkinson's disease (PD) are not completely understood. Here, we use mass spectrometry and microarrays to study the proteomic and transcriptomic changes in the striatum of two mouse models of PD, induced by the distinct neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Proteomic analyses resulted in the identification and relative quantification of 912 proteins with two or more unique peptides and 86 proteins with significant abundance changes following neurotoxin treatment. Similarly, microarray analyses revealed 181 genes with significant changes in mRNA, following neurotoxin treatment. The combined protein and gene list provides a clearer picture of the potential mechanisms underlying neurodegeneration observed in PD. Functional analysis of this combined list revealed a number of significant categories, including mitochondrial dysfunction, oxidative stress response, and apoptosis. These results constitute one of the largest descriptive data sets integrating protein and transcript changes for these neurotoxin models with many similar end point phenotypes but distinct mechanisms.
Chin
Mark H
MH
Department of Molecular and Medical Pharmacology, Human Genetics, Laboratory of NeuroImaging, Department of Neurology, and Surgery, David Geffen School of Medicine at University of California-Los Angeles (UCLA), Los Angeles, California 90095, USA.
Qian
Wei-Jun
WJ
Wang
Haixing
H
Petyuk
Vladislav A
VA
Bloom
Joshua S
JS
Sforza
Daniel M
DM
Laćan
Goran
G
Liu
Dahai
D
Khan
Arshad H
AH
Cantor
Rita M
RM
Bigelow
Diana J
DJ
Melega
William P
WP
Camp
David G
DG
Smith
Richard D
RD
Smith
Desmond J
DJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020543:Proteome / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D012313:RNA / Q000378:metabolism
D009498:Neurotoxins; D020543:Proteome; D012313:RNA; D004298:Dopamine