Geranylgeranylacetone Prevents Acute Liver Damage after Massive Hepatectomy in Rats through Suppression of a CXC Chemokine GRO1 and Induction of Heat Shock Proteins
| Autor: | Hirofumi Kanemura, Kazuhito Rokutan, Seiki Tashiro, Hidenori Miyake, Mitsuo Shimada, Kenji Kusumoto |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Chemokine CXCL1 medicine.medical_treatment Blotting Western Gene Expression Pharmacology Downregulation and upregulation Hsp27 Heat shock protein Gene expression Animals Hepatectomy Medicine HSP70 Heat-Shock Proteins Inducer Rats Wistar Dose-Response Relationship Drug biology Reverse Transcriptase Polymerase Chain Reaction business.industry Endoplasmic reticulum Gastroenterology Liver Failure Acute Anti-Ulcer Agents Microarray Analysis Rats Hsp70 Disease Models Animal Immunology biology.protein Autoradiography RNA Surgery Diterpenes business |
| Zdroj: | Journal of Gastrointestinal Surgery. 13:66-73 |
| ISSN: | 1873-4626 1091-255X |
| DOI: | 10.1007/s11605-008-0604-x |
| Popis: | Acute liver failure after massive hepatectomy remains a challenging problem. In this study, using a microarray designed to monitor the side effects of drugs, we examined changes in gene expression in the remnant liver during the 24 h after hepatectomy and the effects of a nontoxic heat shock protein (HSP) 70 inducer, geranylgeranylacetone (GGA), after 90% hepatectomy in rats. A single oral administration of 100 mg/kg GGA significantly suppressed the release of aminotransferases and improved survival compared with vehicle administration. The hepatectomy upregulated 74 genes and downregulated 95. Interestingly, ten cytokine genes were upregulated, while no cytokine-related gene was downregulated. Among the ten cytokine genes, a potent chemoattractant for neutrophils, GRO1, was most rapidly and markedly upregulated after 90% hepatectomy. GGA effectively suppressed the up-regulation of GRO1 messenger ribonucleic acid, and this was validated by Northern hybridization. Microarray and immunoblot analyses showed that, in addition to HSP70 and HSP27, GGA preferentially induced an endoplasmic reticulum chaperone, BIP. Considering hemodynamic and metabolic overloading as a primary cause of acute lever failure, the ER stress response enhanced by GGA may also play an important role in the prevention of overload-induced liver damage. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink