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
M. Kato1, S. Kato2, Y. Abe3, T. Nishino3, E. Ohama2, M. Aoki4 and Y. Itoyama4
1Division of Pathology, Tottori University Hospital, 2Department of Neuropathology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan, 3Department of Biochemistry and Molecular Biology, Nippon Medical School, Tokyo and 4Department of Neuroscience, Division of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Offprint requests to: Masako Kato, M.D., Ph.D., Division of Pathology, Tottori University Hospital, Nishi-cho 36-1, Yonago 683-8504, Japan. e-mail: makato@grape.med.tottori-u.ac.jp, Shinsuke Kato, M.D., Ph.D., Department of Neuropathology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Nishi-cho 36-1, Yonago 683-8504, Japan. e-mail: kato@grape.med.tottori-u.ac.jp
Summary. 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. Histol Histopathol 21, 729-742 (2006)
Key words: Amyotrophic lateral sclerosis, Hepatocyte, Redox system, Peroxiredoxin, Superoxide dismutase1
DOI: 10.14670/HH-21.729