title: Decrease of Hsp25 protein expression precedes degeneration of motoneurons in ALS-SOD1 mice.
abstract: We have investigated the expression of Hsp25, a heat shock protein constitutively expressed in motoneurons, in amyotrophic lateral sclerosis (ALS) mice that express G93A mutant SOD1 (G93A mice). Immunocytochemistry and Western blotting showed that a decrease of Hsp25 protein expression occurred in motoneurons of G93A mice prior to the onset of motoneuron death and muscle weakness. This decrease in Hsp25 expression also preceded the appearance of SOD1 aggregates as identified by cellulose acetate filtration and Western blot analysis. In contrast to Hsp25 protein levels, Hsp25 mRNA as determined by in situ hybridization and RT-PCR, remained unchanged. This suggests that the decrease in Hsp25 protein levels occurs post-transcriptionally. In view of the cytoprotective properties of Hsp25 and the temporal relationship between decreased Hsp25 expression and the onset of motoneuron death, it is feasible that reduced Hsp25 concentration contributes to the degeneration of motoneurons in G93A mice. These data are consistent with the idea that mutant SOD1 may reduce the availability of the protein quality control machinery in motoneurons.
authors.affiliation: Department of Neuroscience, EE12.10, Erasmus University Rotterdam, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
authors.forename: Arjen
authors.initials: A
authors.lastname: Maatkamp
authors.forename: Angela
authors.initials: A
authors.lastname: Vlug
authors.forename: Elize
authors.initials: E
authors.lastname: Haasdijk
authors.forename: Dirk
authors.initials: D
authors.lastname: Troost
authors.forename: Pim J
authors.initials: PJ
authors.lastname: French
authors.forename: Dick
authors.initials: D
authors.lastname: Jaarsma
mesh_terms: D051700:Activating Transcription Factor 3; D000328:Adult; D000367:Age Factors; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western / Q000379:methods; D016022:Case-Control Studies; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods / Q000706:statistics & numerical data; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D018832:Molecular Chaperones; D009046:Motor Neurons / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism*; D011180:Postmortem Changes; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D051700:Activating Transcription Factor 3; C103002:Atf3 protein, mouse; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C000606290:SOD1 protein, human; D014157:Transcription Factors; D025801:Ubiquitin; C109415:SOD1 G93A protein; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D002795:Choline O-Acetyltransferase