Prominent stress response of Purkinje cells in Creutzfeldt-Jakob disease.
To examine the role of stress-related 70-kDa heat shock proteins (Hsp-s) in Creutzfeldt-Jakob disease (CJD), we performed immunocytochemistry to detect Hsp-72 and Hsp-73, together with the abnormal (PrP(Sc)) and the presumed cellular form (PrP(C)) of the prion protein, and TUNEL method to measure cellular vulnerability in different brain regions in CJD and control cases. While Hsp-73 showed uniform distribution in all the examined samples, an increase in the number of Purkinje cells with prominent accumulation of Hsp-72 in the CJD group was observed. These neurons also showed intense PrP(C) staining, but TUNEL-positive nuclei were only detected in the granular (Hsp-72-negative) cell layer. Fewer cells of the inferior olivary nucleus were immunoreactive for Hsp-72 in CJD than in control cases, and regions showing severe spongiform change and gliosis exhibited fewer Hsp-72-immunoreactive neurons. Our results indicate that accumulation of the inducible Hsp-72 in certain cell types may be part of a cytoprotective mechanism, which includes preservation of proteins like PrP(C).
Kovács
G G
GG
Department of Neurology, Semmelweis University of Medicine, Budapest, Hungary.
Kurucz
I
I
Budka
H
H
Adori
C
C
Müller
F
F
Acs
P
P
Klöppel
S
S
Schätzl
H M
HM
Mayer
R J
RJ
László
L
L
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005911:Gliosis / Q000378:metabolism; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009847:Olivary Nucleus / Q000378:metabolism; D018621:PrPC Proteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D017510:Protein Folding; D011689:Purkinje Cells / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*
D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006360:Heat-Shock Proteins; D009419:Nerve Tissue Proteins; D018621:PrPC Proteins