title: Remarkable reduction of MAP2 in the brains of scrapie-infected rodents and human prion disease possibly correlated with the increase of calpain.
abstract: Microtubule-associated protein 2 (MAP2) belongs to the family of heat stable MAPs, which takes part in neuronal morphogenesis, maintenance of cellular architecture and internal organization, cell division and cellular processes. To obtain insight into the possible alteration and the role of MAP2 in transmissible spongiform encephalopathies (TSEs), the MAP2 levels in the brain tissues of agent 263K-infected hamsters and human prion diseases were evaluated. Western blots and IHC revealed that at the terminal stages of the diseases, MAP2 levels in the brain tissues of scrapie infected hamsters, a patient with genetic Creutzfeldt-Jakob disease (G114V gCJD) and a patient with fatal familial insomnia (FFI) were almost undetectable. The decline of MAP2 was closely related with prolonged incubation time. Exposure of SK-N-SH neuroblastoma cell line to cytotoxic PrP106-126 peptide significantly down-regulated the cellular MAP2 level and remarkably disrupted the microtubule structure, but did not alter the level of tubulin. Moreover, the levels of calpain, which mediated the degradation of a broad of cytoskeletal proteins, were significantly increased in both PrP106-126 treated SK-N-SH cells and brain tissues of 263K prion-infected hamsters. Our data indicate that the decline of MAP2 is a common phenomenon in TSEs, which seems to occur at an early stage of incubation period. Markedly increased calpain level might contribute to the reduction of MAP2.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Han-Shi
authors.initials: HS
authors.lastname: Gong
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Wu-Ling
authors.initials: WL
authors.lastname: Xie
authors.forename: Chan
authors.initials: C
authors.lastname: Tian
authors.forename: Cao
authors.initials: C
authors.lastname: Chen
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Shao-Bin
authors.initials: SB
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Xu
authors.forename: Bao-Yun
authors.initials: BY
authors.lastname: Zhang
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002154:Calpain / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D034062:Insomnia, Fatal Familial / Q000378:metabolism; D008647:Mesocricetus; D018613:Microscopy, Confocal; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D018620:PrPSc Proteins / Q000494:pharmacology; D017096:Prion Diseases / Q000378:metabolism*; D012376:Rodent Diseases / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D018620:PrPSc Proteins; D002154:Calpain