title: Abnormally upregulated αB-crystallin was highly coincidental with the astrogliosis in the brains of scrapie-infected hamsters and human patients with prion diseases.
abstract: αB-crystallin is a member of the small heat shock protein family constitutively presenting in brains at a relatively low level. To address the alteration of αB-crystallin in prion disease, the αB-crystallin levels in the brains of scrapie agent 263 K-infected hamsters were analyzed. The levels of αB-crystallin were remarkably increased in the brains of 263 K-infected hamsters, showing a time-dependent manner along with incubation time. Immunohistochemical (IHC) and immunofluorescent (IFA) assays illustrated more αB-crystallin-positive signals in the regions of the cortex and thalamus containing severe astrogliosis. Double-stained IFA verified that the αB-crystallin signals colocalized with the enlarged glial fibrillary acidic protein-positive astrocytes, but not with neuronal nuclei-positive cells. IHC and IFA of the serial brain sections of infected hamsters showed no colocalization and correlation between PrP(Sc) deposits and αB-crystallin increase. Moreover, increased αB-crystallin deposits were observed in the brain sections of parietal lobe of a sporadic Creutzfeldt-Jakob disease (sCJD) case, parietal lobe and thalamus of a G114V genetic CJD case, and thalamus of a fatal family insomnia (FFI) case, but not in a parietal lobe of FFI where only very mild astrogliosis was addressed. Additionally, the molecular interaction between αB-crystallin and PrP was only observed in the reactions of recombinant proteins purified from Escherichia coli, but not either in that of brain homogenates or in that of the cultured cell lysates expressing human PrP and αB-crystallin. Our data indicate that brain αB-crystallin is abnormally upregulated in various prion diseases, which is coincidental with astrogliosis. Direct interaction between αB-crystallin and PrP seems not to be essential during the pathogenesis of prion infection.
authors.affiliation: School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, People's Republic of China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.forename: Yin
authors.initials: Y
authors.lastname: Xu
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Wu-Ling
authors.initials: WL
authors.lastname: Xie
authors.forename: Yu-E
authors.initials: YE
authors.lastname: Yan
authors.forename: Bao-Yun
authors.initials: BY
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Dong
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis; D057809:HEK293 Cells; D006801:Humans; D009474:Neurons / Q000378:metabolism; D009928:Organ Specificity; D018620:PrPSc Proteins / Q000378:metabolism*; D017096:Prion Diseases / Q000378:metabolism*; D015854:Up-Regulation; D038203:alpha-Crystallin B Chain / Q000235:genetics / Q000378:metabolism*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018620:PrPSc Proteins; D038203:alpha-Crystallin B Chain