Immunohistochemical studies on the expression pattern of molecular chaperones HSC70 and HSP25 and cell cycle-related proteins cyclin D1 and PCNA in rat liver after thioacetamide intoxication.
Intoxication of rats with thioacetamide (TAA) is a model system to investigate mechanisms involved in liver cell death and tissue reconstitution. Our study was undertaken to determine by immunohistochemistry the expression pattern of the cytoprotective chaperone proteins HSC70 and HSP25 and proliferation markers cyclin D1 and PCNA in livers of Wistar rats intraperitoneally injected with TAA at a single dose of 50 mg/kg. For each protein studied we observed distinct dynamic changes in appearance and localization in liver lobules. During 24-36 h after TAA injection the HSC70 cytoplasmic immunoreaction gradually disappeared from hepatocytes localized around central veins and a shift of immunostaining to cell nuclei took place. Then, 36-48 h after TAA injection the HSC70 cytoplasmic immunoreaction reappeared with the highest intensity in hepatocytes surrounding the areas of inflammatory cells. HSP25, undetectable in control hepatocytes began to appear at approximately 36 h after TAA injection and HSP25-immunopositive cells formed a characteristic ring around areas of inflammation. Of the proteins studied, the most rapid reaction to TAA was observed for cyclin D1. As early as 15 min after TAA administration cyclin D1-positive hepatocytes appeared in intermediate and periportal areas of liver lobules and a subsequent shift of staining to centrilobular hepatocytes took place at 36 and 48 h. There was no correlation of cyclin D1 localization either with PCNA-positive cells or mitotic cells. Our observations suggest that in TAA-treated livers HSP25 and HSC70 proteins can play an anti-inflammatory role, and the early and distinct cyclin D1 expression is not related to proliferation of hepatocytes.
Zborek
Anna
A
Department of Tumor Biology, Centre of Oncology, Maria Skłodowska-Curie Memorial Institute, Wybrzee Armii Krajowej 15, 44-100 Gliwice, Poland.
Małusecka
Ewa
E
Krzyowska-Gruca
Stefania
S
Wysocka
Aleksandra
A
Krawczyk
Zdzisław
Z
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism*; D004195:Disease Models, Animal; D050883:HSC70 Heat-Shock Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins; D007124:Immunoenzyme Techniques; D007274:Injections, Intraperitoneal; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009363:Neoplasm Proteins / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013853:Thioacetamide / Q000008:administration & dosage / Q000633:toxicity; D013997:Time Factors
D050883:HSC70 Heat-Shock Proteins; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C494373:Hspa8 protein, rat; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D013853:Thioacetamide; D019938:Cyclin D1