Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure.

Hiromi Fujii, Toru Takahashi, Masaki Matsumi, Ryuji Kaku, Hiroko Shimizu, Masataka Yokoyama, Emiko Ohmori, Takahito Yagi, Hiroshi Sadamori, Noriaki Tanaka, Reiko Akagi, Kiyoshi Morita

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13 Citations (Scopus)

Abstract

Acute liver failure (ALF) remains a serious problem in critical care with a high rate of mortality. Although the pathophysiology of ALF has not been fully elucidated, oxidative stress has been in part implicated in its pathogenesis. Heme oxygenase-1 (HO-1) is known to be induced not only by its substrate, heme, but also by various oxidative stresses, and thought to play an important role in the protection of the host from oxidative tissue injuries. In the present study, we examined expression of HO-1 as well as the non-specific delta-aminolevulinate synthase (ALAS-N, or ALAS1), the rate-limiting enzyme in heme catabolism and biosynthesis, respectively, in the livers of patients with ALF. Compared with livers from control subjects who had various disorders, but normal hepatic function, HO-1 in the liver of ALF patients was highly up-regulated at both transcriptional and protein levels. Immunohistochemical studies demonstrated that HO-1 expression occurred predominantly in hepatocytes, but not in non-parenchymal cells. In contrast to HO-1, ALAS1 gene expression was markedly down-regulated in ALF patients compared with controls. These findings suggest that, in the liver of ALF patients, there may be an increase in free heme concentration which up-regulates HO-1 gene expression, while down-regulating ALAS1 gene expression, resulting in markedly altered heme metabolism and liver function.

Original languageEnglish
Pages (from-to)1001-1005
Number of pages5
JournalInternational journal of molecular medicine
Volume14
Issue number6
Publication statusPublished - Dec 2004

ASJC Scopus subject areas

  • Genetics

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    Fujii, H., Takahashi, T., Matsumi, M., Kaku, R., Shimizu, H., Yokoyama, M., Ohmori, E., Yagi, T., Sadamori, H., Tanaka, N., Akagi, R., & Morita, K. (2004). Increased heme oxygenase-1 and decreased delta-aminolevulinate synthase expression in the liver of patients with acute liver failure. International journal of molecular medicine, 14(6), 1001-1005.