Carbon monoxide as a guardian against hepatobiliary dysfunction

Makoto Suematsu, Kosuke Tsukada, Toshihide Tajima, Takehiro Yamamoto, Daigo Ochiai, Hiroshi Watanabe, Yasunori Yoshimura, Nobuhito Goda

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6 Citations (Scopus)

Abstract

Carbon monoxide (CO) generated through the reaction of heme oxygenase (HO) has attracted great interest in regulation of hepatobiliary homeostasis. The gas generated by HO-2 in the hepatic parenchyma can modestly activate soluble guanylate cyclase (sGC) expressed in hepatic stellate cells in a paracrine manner and thereby constitutively relax sinusoids. Kupffer cells express HO-1, the inducible isozyme, even under normal unstimulated conditions and constitutes approximately 30% of the total HO activity in this organ. Upon exposure to a variety of stressors such as cytokines, endotoxin, hypoxia and oxidative stress, the liver induces HO-1 and overproduces CO. The stress-inducible CO has been shown to guarantee ample blood supply during detoxification of heme and thus to play a protective role in the liver. However, molecular mechanisms by which CO serves as a protectant for hepatocytes, the cells expressing little sGC, remain to be solved. Previous observation suggested that CO modulates intracellular calcium mobilization through inhibiting cytochrome P-450 activities and thereby maintain stroke volume of bile canalicular contraction in cultured hepatocytes. CO also stimulates mrp2-dependent excretion of bilirubin-IXα and helps heme catabolism. Although a direct molecular target responsible for the latter event remains unknown, such properties of CO could support xenobiotic metabolism through its actions on sinusoidal hemodynamics and hepatobiliary systems.

Original languageEnglish
JournalAlcoholism: Clinical and Experimental Research
Volume29
Issue number11 SUPPL.
DOIs
Publication statusPublished - 2005 Nov
Externally publishedYes

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Keywords

  • Carbon monoxide
  • Gas Biology
  • Heme Oxygenase
  • Metabolome
  • Soluble Guanylate Cyclase
  • Xenobiotic Metabolism

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Suematsu, M., Tsukada, K., Tajima, T., Yamamoto, T., Ochiai, D., Watanabe, H., Yoshimura, Y., & Goda, N. (2005). Carbon monoxide as a guardian against hepatobiliary dysfunction. Alcoholism: Clinical and Experimental Research, 29(11 SUPPL.). https://doi.org/10.1097/01.alc.0000189273.49148.87