Pivotal role of attractin in cell survival under oxidative stress in the zitter rat brain with genetic spongiform encephalopathy.
Accumulation of reactive oxygen species (ROS), which is generated during energy metabolism, is a cause of physiological aging, neuropathogenesis and numerous diseases, such as Parkinson's and Alzheimer's diseases. Zitter rat is an autosomal recessive mutant, characterized by spongiform degeneration and hypomyelination in the brain, and the phenotype has been suggested to be involved in oxidative stress by the accumulation of ROS. To determine the relation between neurodegeneration of the zitter rat and Attractin (Atrn) gene expression, which was identified as a gene responsible for the zitter, we established fibroblast cells from the zitter rat (Fz) and the Wistar tremor control (WTC) rat (Fw), and transduced Fz cells with the Atrn gene (Fz/Atrn). In the Fz/Atrn cells, accumulation of ROS was repressed, and cell survival against oxidative stress was enhanced to the same level as in Fw cells. Interestingly, phosphorylation of ERK was significantly increased in Fz/Atrn cells by H(2)O(2) stimulus, similarly to Fw cells. Furthermore, activation of ERK was confirmed in the brains of WTC and zitter rats by Western blot analysis and immunohistochemistry. These observations suggested that lack of Atrn gene expression induced neurodegeneration by a decrease in active ERK through an intracellular signaling via oxidative stress.
Muto
Yuri
Y
Division of Molecular Biology, Department of Molecular and Cellular Biology, School of Life Sciences, Tottori University Faculty of Medicine, Nishimachi 86, Yonago 683-8503, Japan.
Sato
Kenzo
K
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D020271:Heredodegenerative Disorders, Nervous System / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D010766:Phosphorylation; D051381:Rats; D011922:Rats, Mutant Strains; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015854:Up-Regulation / Q000235:genetics
C492191:Atrn protein, rat; D016166:Free Radical Scavengers; D008565:Membrane Proteins; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases