Tissue-specific gene expression of heme oxygenase-1 (HO-1) and non-specific delta-aminolevulinate synthase (ALAS-N) in a rat model of septic multiple organ dysfunction syndrome
| Autor: | Tadao Fujiwara, Reiko Akagi, Masahisa Hirakawa, Akira Yamasaki, Tsutomu Suzuki, Toru Takahashi |
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| Rok vydání: | 2000 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Time Factors Lipopolysaccharide Multiple Organ Failure Oxidative phosphorylation Heme Biology Kidney Biochemistry Gene Expression Regulation Enzymologic Sepsis Rats Sprague-Dawley chemistry.chemical_compound Internal medicine Gene expression medicine Animals RNA Messenger Pharmacology medicine.disease Rats Heme oxygenase Disease Models Animal medicine.anatomical_structure Endocrinology chemistry Liver Immunology Heme Oxygenase (Decyclizing) Multiple organ dysfunction syndrome Heme Oxygenase-1 5-Aminolevulinate Synthetase |
| Zdroj: | Biochemical pharmacology. 60(2) |
| ISSN: | 0006-2952 |
| Popis: | Reactive oxygen species are thought to be involved in the pathogenesis of septic multiple organ dysfunction syndrome (MODS). It has been reported that heme oxygenase-1 (HO-1) (EC 1.14.99.3) is induced in septic animal models and is thought to confer protection against oxidative tissue injury. In this study, we examined changes in gene expression of HO-1 and non-specific δ-aminolevulinate synthase (ALAS-N) (EC 2.3.1.37), the rate-limiting enzymes in heme catabolism and heme synthesis, respectively, after intraperitoneal administration of bacterial lipopolysaccharide (LPS) to rats. LPS treatment caused the elevation of body temperature, increases in white blood cell counts, and marked elevation of serum interleukin-6 levels associated with liver, lung, and kidney injuries, characteristic of septic MODS. LPS administration significantly induced HO-1 mRNA, protein, and enzyme activity in the liver, lung, and kidney. In contrast, ALAS-N mRNA was decreased rapidly in the liver, followed by an oscillating recovery pattern. Induction of hepatic HO-1 mRNA and rapid suppression of ALAS-N mRNA were likely the result of a rapid increase in hepatic free heme concentration as judged by the increase in heme saturation of tryptophan pyrrolase. In contrast to that in the liver, the ALAS-N mRNA level in the lung and kidney was increased significantly after LPS administration, suggesting a novel mechanism of ALAS-N regulation in these tissues. These findings suggest that HO-1 and ALAS-N mRNA are regulated in a tissue-specific manner in a rat model of septic MODS. |
| Databáze: | OpenAIRE |
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