Carbon monoxide as a guardian against hepatobiliary dysfunction

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


研究成果: Article査読

7 被引用数 (Scopus)


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.

ジャーナルAlcoholism: Clinical and Experimental Research
出版ステータスPublished - 2005 11月

ASJC Scopus subject areas

  • 医学(その他)
  • 毒物学
  • 精神医学および精神衛生


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