title: Changes in HSP gene and protein expression in natural scrapie with brain damage.
abstract: Heat shock proteins (Hsp) perform cytoprotective functions such as apoptosis regulation and inflammatory response control. These proteins can also be secreted to the extracellular medium, acting as inflammatory mediators, and their chaperone activity permits correct folding of proteins and avoids the aggregation of anomalous isoforms. Several studies have proposed the implication of Hsp in prion diseases. We analysed the gene expression and protein distribution of different members of the Hsp27, Hsp70, and Hsp90 families in the central nervous system of sheep naturally infected with scrapie. Different expression profiles were observed in the areas analysed. Whereas changes in transcript levels were not observed in the cerebellum or medulla oblongata, a significant decrease in HSP27 and HSP90 was detected in the prefrontal cortex. In contrast, HSP73 was over-expressed in diencephalons of scrapie animals. Western blotting did not reveal significant differences in Hsp90 and Hsp70 protein expression between scrapie and control animals. Expression rates identified by real-time RT-PCR and western blotting were compared with the extent of classical scrapie lesions using stepwise regression. Changes in Hsp gene and protein expression were associated with prion protein deposition, gliosis and spongiosis rather than with apoptosis. Finally, immunohistochemistry revealed intense Hsp70 and Hsp90 immunolabelling in Purkinje cells of scrapie sheep. In contrast, controls displayed little or no staining in these cells. The observed differences in gene expression and protein distribution suggest that the heat shock proteins analysed play a role in the natural form of the disease.
authors.affiliation: Laboratorio de Genética Bioquímica (LAGENBIO), Facultad de Veterinaria, Universidad de Zaragoza, Miguel Servet 177, 50013 Zaragoza, Spain. minma@unizar.es.
authors.forename: Carmen
authors.initials: C
authors.lastname: Serrano
authors.forename: Rosa
authors.initials: R
authors.lastname: Bolea
authors.forename: Jaber
authors.initials: J
authors.lastname: Lyahyai
authors.forename: Hicham
authors.initials: H
authors.lastname: Filali
authors.forename: Luis
authors.initials: L
authors.lastname: Varona
authors.forename: Ane
authors.initials: A
authors.lastname: Marcos-Carcavilla
authors.forename: Cristina
authors.initials: C
authors.lastname: Acín
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Calvo
authors.forename: Magdalena
authors.initials: M
authors.lastname: Serrano
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Badiola
authors.forename: Pilar
authors.initials: P
authors.lastname: Zaragoza
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Martín-Burriel
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D002418:Cattle Diseases / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000662:veterinary; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000662:veterinary; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012756:Sheep
chemical_list: D006360:Heat-Shock Proteins; D011328:Prions