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.

Abstract

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 delta-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.

• Authors: T Suzuki, T Takahashi, A Yamasaki, T Fujiwara, M Hirakawa, R Akagi
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 60 Issue 2 Pg. 275-83 (Jul 15 2000) ISSN: 0006-2952 [Print] England
• PMID: 10825473 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipopolysaccharides
• RNA, Messenger
• Heme
• Heme Oxygenase (Decyclizing)
• Heme Oxygenase-1
• 5-Aminolevulinate Synthetase

Topics

• 5-Aminolevulinate Synthetase (genetics, metabolism)
• Animals
• Disease Models, Animal
• Gene Expression Regulation, Enzymologic (drug effects)
• Heme (metabolism)
• Heme Oxygenase (Decyclizing) (genetics, metabolism)
• Heme Oxygenase-1
• Kidney (metabolism)
• Lipopolysaccharides (pharmacology)
• Liver (metabolism)
• Male
• Multiple Organ Failure (enzymology, etiology, genetics)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Sepsis (chemically induced, complications)
• Time Factors