Proteome analysis of ventral midbrain in MPTP-treated normal and L1cam transgenic mice.
Treatment of mice by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridene hydrochloride (MPTP) is a well established animal model for Parkinson's disease (PD), while overexpression of L1 cell adhesion molecule (L1cam) has been proposed to attenuate the degeneration of dopaminergic neurons induced by MPTP. To gain insight into the role of L1cam in the pathomechanism of PD, we investigated protein expression patterns after MPTP-treatment in both C57BL/6 (wild-type) and transgenic mice overexpressing L1cam in astrocytes. Our results showed that during the acute phase, proteins in functional complexes responsible for mitochondrial, glycolysis, and cytoskeletal function were down-regulated in MPTP-treated wild-type mice. After a recovery phase, proteins that were down-regulated in the acute phase reverted to normal levels. In L1cam transgenic mice, a much higher number of proteins was altered during the acute phase and this number even increased after the recovery phase. Many proteins involved in oxidative phosphorylation were still down-regulated and glycolysis related protein were still up-regulated. This pattern indicates a lasting severely impaired energy production in L1cam mice after MPTP treatment.
Diedrich
Madeleine
M
Institute for Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.
Mao
Lei
L
Bernreuther
Christian
C
Zabel
Claus
C
Nebrich
Grit
G
Kleene
Ralf
R
Klose
Joachim
J
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D015152:Blotting, Northern; D003599:Cytoskeleton / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D006019:Glycolysis; D020267:MPTP Poisoning / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D020543:Proteome / Q000032:analysis*; D025801:Ubiquitin / Q000378:metabolism
D039842:Neural Cell Adhesion Molecule L1; D020543:Proteome; D025801:Ubiquitin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine