title: Histological recovery of the hepatocytes is based on the redox system upregulation in the animal models of mutant superoxide dismutase (SOD)1-linked amyotrophic lateral sclerosis.
abstract: Histological rescue of superoxide dismutase1 (SOD1)-mutated hepatocytes from mutant SOD1 stress is investigated from the viewpoint of upregulation of the redox system [peroxiredoxin (Prx) and glutathione peroxidase (GPx)]. Histopathological and immunohistochemical studies using antibodies against PrxI/PrxII/GPxI were carried out on specimens from four different strains of animal models of mutant SOD1-linked familial amyotrophic lateral sclerosis (ALS). In the livers of the ALS animal models in the presymptomatic stage without motor neuron loss, both swollen and eosinophilic hepatocytes with vacuolation pathology were observed. After developing motor deficits, this swelling and vacuolation ceased to be apparent. In the terminal stage when severe motor neuron loss was observed, these hepatocytes recovered and appeared normal. In redox system-related immunohistochemical preparations, almost all of the normal hepatocytes expressed the redox system-related enzymes PrxI/PrxII/GPxI. In the presymptomatic stage, some hepatocytes did not express redox system-related enzymes. After clinical onset, over 75% of hepatocytes showed overexpression of PrxI/PrxII/GPxI, i. e., upregulation of the redox system. At the end stage, near normal PrxI/PrxII/GPxI expression was observed again in the hepatocytes. Redox system upregulation in SOD1-mutated hepatocytes rescues hepatocytes from the mutant SOD1 stress that leads to motor neuron death.
authors.affiliation: Division of Pathology, Tottori University Hospital, Nishi-cho 36-1, Yonago 683-8504, Japan. makato@grape.med.tottori-u.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Abe
authors.forename: T
authors.initials: T
authors.lastname: Nishino
authors.forename: E
authors.initials: E
authors.lastname: Ohama
authors.forename: M
authors.initials: M
authors.lastname: Aoki
authors.forename: Y
authors.initials: Y
authors.lastname: Itoyama
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D022781:Hepatocytes / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D000072105:Superoxide Dismutase-1; D015854:Up-Regulation; D000094765:Glutathione Peroxidase GPX1
chemical_list: D006360:Heat-Shock Proteins; C000606290:SOD1 protein, human; D010544:Peroxidases; C489898:Prdx1 protein, rat; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; D005979:Glutathione Peroxidase; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1