title: Heat shock protein 70 kDa over-expression and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced nigrostriatal degeneration in mice.
abstract: Oxidative damage in the dopaminergic neurons of substantia nigra pars compacta (SNpc) plays an important role in the pathogenesis of Parkinson's disease (PD). Heat shock proteins 70 kDa (HSP70s) are a sub-family of molecular chaperones involved in not only protein folding and degradation but also antioxidant defense and anti-apoptotic pathways. Here, a transgenic mice over-expressing an inducible form of Hsp70 was used to determine whether HSP70 affects 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal degeneration, an experimental model of PD. The Hsp70 transgenic animals exhibited a high level of expression of HSP70 protein in ventral mesencephalon. Dopaminergic cell death in the SNpc was similar between wild-type and Hsp70 transgenic mice with either acute (40 mg/kg, single dose) or chronic (20 mg/kg, three times/week during 1 month) MPTP treatment. In addition, striatal dopamine loss was not different between wild-type and transgenic animals. Three months after the acute MPTP treatment, dopamine loss was partially recovered into a similar level between wild-type and transgenic groups. In conclusion, over-expression of Hsp70 does not suppress dopaminergic neuronal damage at either the somata or the axon terminals of dopaminergic neurons. Hsp70 over-expression does not help axon terminal regeneration either. These results indicate that HSP70 alone is not sufficient to reduce MPTP-induced dopaminergic neuronal damage.
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Seville, Spain. lgao-ibis@us.es
authors.forename: L
authors.initials: L
authors.lastname: Gao
authors.forename: J
authors.initials: J
authors.lastname: Díaz-Martín
authors.forename: W H
authors.initials: WH
authors.lastname: Dillmann
authors.forename: J
authors.initials: J
authors.lastname: López-Barneo
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D016755:Proto-Oncogene Proteins c-jun; D015102:3,4-Dihydroxyphenylacetic Acid; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid