Transcription factors C/EBP-alpha and HNF-1 alpha are associated with decreased expression of liver-specific genes in sepsis
| Autor: | Haaxma, CA, Kim, PK, Andrejko, KM, Raj, NR, Deutschman, CS |
|---|---|
| Přispěvatelé: | Faculteit Medische Wetenschappen/UMCG |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
MULTIPLE ORGAN FAILURE
GLUCOSE-6-PHOSPHATASE GENE CARNITINE-PALMITOYLTRANSFERASE ornithine transcarbamylase Mrp2 5'-FLANKING REGION C/EBP Ntcp carnitine palmitoyltransferase II SYSTEMIC INFLAMMATORY RESPONSE digestive system sepsis systemic inflammatory response syndrome HNF-1 FUNCTIONAL-CHARACTERIZATION HNF-3 PHOSPHOENOLPYRUVATE CARBOXYKINASE GENE CCAAT/ENHANCER-BINDING PROTEIN NUCLEAR FACTOR-I ACID COTRANSPORTER |
| Zdroj: | Shock, 19(1), 45-49. LIPPINCOTT WILLIAMS & WILKINS |
| ISSN: | 1073-2322 |
| Popis: | Previous studies have demonstrated sepsis-specific changes in the transcription of key hepatic genes. However, the role of hepatic transcription factors in sepsis-associated organ dysfunction has not been well established. We hypothesize that the binding activities of C/EBPalpha and beta, HNF-1alpha, and HNF-3 transiently decrease during mild sepsis but persistently decrease after fulminant sepsis, and that the decrease in this binding activity correlates in time and severity with previously described decreases in the transcription of key hepatic genes. Male C57/BL6 mice had nonlethal sepsis induced by cecal ligation and single puncture (CLP) and fulminant sepsis via cecal ligation and double puncture (2CLP). Sham-operated and unoperated animals served as controls. Transcription factor binding activity was assessed with electrophoretic mobility shift assays. C/EBP-alpha and HNF-1alpha binding activity decreased transiently after CLP and persistently after 2CLP. Binding activity of both C/EBP-beta and HNF-3 were unchanged. The decrease in C/EBP-a and HNF-1alpha binding activities correlated in time and magnitude with the decreased hepatic gene transcription previously observed in sepsis. Furthermore, the loss of activity after 2CLP correlated in time with outcome. Sepsis decreases DNA binding activities of C/EBPalpha and HNF-1alpha, two key hepatocyte transcription factors, in a time course consistent with down-regulation of their target hepatic genes. Therefore, alterations in transcription factor binding are likely important in the transcriptional modulation that is characteristic of hepatic dysfunction in sepsis. |
| Databáze: | OpenAIRE |
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