TY - JOUR
T1 - Mesencephalic and striatal protein profiles in mice over-expressing glucose-6-phosphate dehydrogenase in dopaminergic neurons
AU - Romero-Ruiz, Antonio
AU - Mejías, Rebeca
AU - Díaz-Martín, Juan
AU - López-Barneo, José
AU - Gao, Lin
PY - 2010/8
Y1 - 2010/8
N2 - Oxidative damage in dopaminergic neurons of the substantia nigra plays an important role in the pathogenesis of Parkinson's disease. Glucose-6-phosphate dehydrogenase (G6PD) is a key protective enzyme responsible for maintaining adequate levels of the major cellular reducing agent NADPH. We have previously shown that over-expression of G6PD in dopaminergic neurons of the substantia nigra results in resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. In order to further examine this neuroprotective effect, a comparative proteomic study of the ventral mesencephalon (containing substantia nigra) and the striatum between wild-type and G6PD over-expressing mice was carried out. In addition to the protein level, over-expression of G6PD in the transgenic animals was also confirmed by determination of mRNA and enzymatic activity. Proteins with differential expression were mainly involved in antioxidant defense, detoxification and synaptic function, as demonstrated by gene ontology analysis. Hence, the changes in the nigrostriatal protein profile could partially explain the protection against MPTP-induced neuronal damage, and could also lead to new potential targets for antioxidant pharmacological intervention.
AB - Oxidative damage in dopaminergic neurons of the substantia nigra plays an important role in the pathogenesis of Parkinson's disease. Glucose-6-phosphate dehydrogenase (G6PD) is a key protective enzyme responsible for maintaining adequate levels of the major cellular reducing agent NADPH. We have previously shown that over-expression of G6PD in dopaminergic neurons of the substantia nigra results in resistance to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in mice. In order to further examine this neuroprotective effect, a comparative proteomic study of the ventral mesencephalon (containing substantia nigra) and the striatum between wild-type and G6PD over-expressing mice was carried out. In addition to the protein level, over-expression of G6PD in the transgenic animals was also confirmed by determination of mRNA and enzymatic activity. Proteins with differential expression were mainly involved in antioxidant defense, detoxification and synaptic function, as demonstrated by gene ontology analysis. Hence, the changes in the nigrostriatal protein profile could partially explain the protection against MPTP-induced neuronal damage, and could also lead to new potential targets for antioxidant pharmacological intervention.
KW - Antioxidant defense
KW - Glucose-6-phosphate dehydrogenase
KW - Parkinson's disease
KW - Proteomics
KW - Transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=77954660152&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954660152&partnerID=8YFLogxK
U2 - 10.1016/j.jprot.2010.05.014
DO - 10.1016/j.jprot.2010.05.014
M3 - Article
C2 - 20594931
AN - SCOPUS:77954660152
SN - 1874-3919
VL - 73
SP - 1747
EP - 1757
JO - Journal of Proteomics
JF - Journal of Proteomics
IS - 9
ER -