title: Upregulation of HSP27 in a transgenic model of ALS.
abstract: Mutations of the SOD1 gene underlie 1 form of familial amyotrophic lateral sclerosis (ALS). Their pathogenic mechanism remains uncertain, but is thought to involve oxidative stress and abnormal protein aggregation, 2 processes known to induce heat shock proteins (HSPs). We studied the expression of 3 HSPs (alphaB-crystallin, HSP27, and HSP70) in transgenic mice overexpressing human mutant (G93A and G37R) SOD1, using a combination of immunohistochemistry and immunoblotting. Quantitative Western blot analysis demonstrated alphaB-crystallin and HSP27 to be upregulated in the spinal cord of mutant SOD1 mice compared to mice overexpressing wild-type SOD1. HSP70 levels were normal. Immunocytochemical studies of the ventral horn of the spinal cord demonstrated HSP27 to be localized in the nucleus of neurons and glial cells in presymptomatic and early symptomatic animals, where it often was punctate in pattern. In the later stages of the disease, HSP27 was predominantly present in the cytoplasm of reactive glial cells. The early nuclear localization was confirmed by Western blot analysis of spinal cord nuclear and cytoplasmic fractions. In contrast to HSP27, alphaB-crystallin was localized exclusively in the cytoplasm of reactive glial cells.
authors.affiliation: Dept. of Neurology, University of Leuven, Medical School, Belgium.
authors.forename: Vicky
authors.initials: V
authors.lastname: Vleminckx
authors.forename: Philip
authors.initials: P
authors.lastname: Van Damme
authors.forename: Karolien
authors.initials: K
authors.lastname: Goffin
authors.forename: Hans
authors.initials: H
authors.lastname: Delye
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
authors.forename: Wim
authors.initials: W
authors.lastname: Robberecht
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis*; D009457:Neuroglia / Q000473:pathology; D009474:Neurons / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation / Q000502:physiology*; D038203:alpha-Crystallin B Chain / Q000378:metabolism
chemical_list: D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; D018832:Molecular Chaperones; D009363:Neoplasm Proteins; C000606290:SOD1 protein, human; D038203:alpha-Crystallin B Chain; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1