Carbon monoxide as a guardian against hepatobiliary dysfunction

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

Research output: Contribution to journalArticle

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

Fingerprint

Carbon Monoxide
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Guanylate Cyclase
Heme
Liver
Hepatocytes
Hepatic Stellate Cells
Detoxification
Oxidative stress
Kupffer Cells
Hemodynamics
Xenobiotics
Bilirubin
Metabolism
Endotoxins
Bile
Stroke Volume
Cytochrome P-450 Enzyme System
Isoenzymes

Keywords

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

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Carbon monoxide as a guardian against hepatobiliary dysfunction. / Suematsu, Makoto; Tsukada, Kosuke; Tajima, Toshihide; Yamamoto, Takehiro; Ochiai, Daigo; Watanabe, Hiroshi; Yoshimura, Yasunori; Goda, Nobuhito.

In: Alcoholism: Clinical and Experimental Research, Vol. 29, No. 11 SUPPL., 11.2005.

Research output: Contribution to journalArticle

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, vol. 29, no. 11 SUPPL.. https://doi.org/10.1097/01.alc.0000189273.49148.87
Suematsu, Makoto ; Tsukada, Kosuke ; Tajima, Toshihide ; Yamamoto, Takehiro ; Ochiai, Daigo ; Watanabe, Hiroshi ; Yoshimura, Yasunori ; Goda, Nobuhito. / Carbon monoxide as a guardian against hepatobiliary dysfunction. In: Alcoholism: Clinical and Experimental Research. 2005 ; Vol. 29, No. 11 SUPPL.
@article{5e4c248ae0564465a9fff100f31358f5,
title = "Carbon monoxide as a guardian against hepatobiliary dysfunction",
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.",
keywords = "Carbon monoxide, Gas Biology, Heme Oxygenase, Metabolome, Soluble Guanylate Cyclase, Xenobiotic Metabolism",
author = "Makoto Suematsu and Kosuke Tsukada and Toshihide Tajima and Takehiro Yamamoto and Daigo Ochiai and Hiroshi Watanabe and Yasunori Yoshimura and Nobuhito Goda",
year = "2005",
month = "11",
doi = "10.1097/01.alc.0000189273.49148.87",
language = "English",
volume = "29",
journal = "Alcoholism: Clinical and Experimental Research",
issn = "0145-6008",
publisher = "Wiley-Blackwell",
number = "11 SUPPL.",

}

TY - JOUR

T1 - Carbon monoxide as a guardian against hepatobiliary dysfunction

AU - Suematsu, Makoto

AU - Tsukada, Kosuke

AU - Tajima, Toshihide

AU - Yamamoto, Takehiro

AU - Ochiai, Daigo

AU - Watanabe, Hiroshi

AU - Yoshimura, Yasunori

AU - Goda, Nobuhito

PY - 2005/11

Y1 - 2005/11

N2 - 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.

AB - 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.

KW - Carbon monoxide

KW - Gas Biology

KW - Heme Oxygenase

KW - Metabolome

KW - Soluble Guanylate Cyclase

KW - Xenobiotic Metabolism

UR - http://www.scopus.com/inward/record.url?scp=32044436260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=32044436260&partnerID=8YFLogxK

U2 - 10.1097/01.alc.0000189273.49148.87

DO - 10.1097/01.alc.0000189273.49148.87

M3 - Article

VL - 29

JO - Alcoholism: Clinical and Experimental Research

JF - Alcoholism: Clinical and Experimental Research

SN - 0145-6008

IS - 11 SUPPL.

ER -