Skip to main content
SpringerLink
Log in

Carbon Monoxide as a Gaseous Regulator of Liver Microcirculation

  • Conference paper
HCV/Oxidative Stress and Liver Disease

Summary

Carbon monoxide (CO) is synthesized in vivo by heme oxygenase (HO). Recent studies suggest that the liver utilizes this gas to relax its microvessels such as sinusoids and to thereby maintain low vascular resistance. CO seems to be released mainly from hepatocytes that express HO-2, the constitutive enzyme, and also HO-1, induced under stress conditions. CO released into the space of Disse accesses the hepatic stellate cells, which express soluble guanylate cyclase as a gas signal transducer, although whether this heme protein serves as an authentic receptor for CO remains unknown. This chapter focuses on recent developments, collected from both experimental and clinical settings, regarding both the physiologic and pathophysiologic roles of CO as a regulator of hepatobiliary functions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 54.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Tenhunen R, Marver HS, Schmid R (1968) The enzymatic conversion of heure to bilirubin by microsomal heure oxygenase. Proc Natl Acad Sci USA 61: 748–755

    Article  PubMed  CAS  Google Scholar 

  2. Maines MD, Kappas A (1974) Cobalt induction of hepatic heure oxygenase; with evidence that cytochrome P450 is not essential for this enzyme activity. Proc Natl Acad Sci USA 71: 4293–4297

    Article  PubMed  CAS  Google Scholar 

  3. Yoshida T, Kikuchi G (1974) Partial purification and reconstruction of the heure oxygenase system from pig spleen microsomes. Biochem J 75: 1187–1191

    CAS  Google Scholar 

  4. Shibahara S, Muler R, Taguchi H, Yoshida T (1985) Cloning and expression of cDNA of rat heure oxygenase. Proc Natl Acad Sci USA 82: 7865–7869

    Article  PubMed  CAS  Google Scholar 

  5. Maines MD, Trakshel GM, Kutty RK (1986) Characterization of two constitutive forms of rat liver microsomal heure oxygenase: only one molecular species of the enzyme is inducible. J Biol Chem 261: 411–419

    PubMed  CAS  Google Scholar 

  6. Tacchini L, Schiaffonati L, Pappalardo C, Gatti C, Bernelli-Zazzera A (1993) Expression of HSP 70, immediate-early response and heure oxygenase genes in ischemiareperfused rat liver. Lab Invest 68: 465–471

    PubMed  CAS  Google Scholar 

  7. Choi AMK, Alam J (1996) Herne oxygenase-1: function, regulation and implication of a novel stress-inducible protein in oxidant-induced lung injury. Am J Respir Cell Mol Biol 15: 9–19

    PubMed  CAS  Google Scholar 

  8. Rizzardini M, Carelli M, Cabello-Porras MR, Cantoni L (1994) Mechanisms of endotoxin-induced haem oxygenase mRNA accumulation in mouse liver: synergism by glutathione depletion and protection by N-acetylcysteine. Biochem J 304: 477483

    Google Scholar 

  9. Schoendorf TH, Rosenberg M, Beller FK (1971) Endotoxin-induced disseminated intravascular coagulation in nonpregnant rats. A new experimental model. Am J Pathol 65: 51–58

    Google Scholar 

  10. Nath KA, Balla G, Vercellotti GM, Balla J, Jacob HS, Levitt MD, Rosenberg ME (1992) Induction of heme oxygenase is a rapid, protective response in rhabdomyolysis in the rat. J Clin Invest 90: 267–270

    Article  PubMed  CAS  Google Scholar 

  11. Immenschuh S, Hinke V, Ohlmann A, Gifhorn-Katz S, Katz N, Jungermann K, Kietzmann T (1998) Transcriptional activation of the haem oxygenase-1 gene by cGMP via cAMP response element/activator protein-1 element in primary cultures of rat hepatocytes. Biochem J 334: 141–146

    PubMed  CAS  Google Scholar 

  12. Schmidt HW (1992) NO, CO and OH: endogenous soluble guanylyl cyclase activating factors. FEBS Lett 307: 102–107

    Article  PubMed  CAS  Google Scholar 

  13. Liu H, Mount DB, Nasjletti A, Wang W (1999) Carbon monoxide stimulates the apical 70-pS K+ channel of the rat thick ascending limb. J Clin Invest 103: 963–970

    Article  PubMed  CAS  Google Scholar 

  14. Suematsu M, Kashiwagi S, Sano T, Goda N, Shinoda Y, Ishimura Y (1994) Carbon monoxide as an endogenous modulator of hepatic vascular perfusion. Biochem Biophys Res Commun 205: 1333–1337

    Article  PubMed  CAS  Google Scholar 

  15. Suematsu M, Goda N, Sano T, Kashiwagi S, Shinoda Y, Ishimura Y (1995) Carbon monoxide: an endogenous modulator of sinusoidal tone in the perfused rat liver. J Clin Invest 96: 2431–2437

    Article  PubMed  CAS  Google Scholar 

  16. Goda N, Suzuki K, Naito M, Takeoka S, Tsuchida E, Ishimura Y, Tamatani T, Suematsu M (1998) Distribution of heme oxygenase isoforms in rat liver: Topographic basis for carbon monoxide-mediated microvascular relaxation. J Clin Invest 101: 604–612

    Google Scholar 

  17. Shinoda Y, Suematsu M, Wakabayashi Y, Goda N, Suzuki T, Saito S, Yamaguchi T, Ishimura Y (1998) Carbon monoxide as a regulator of bile canalicular contractility in cultured rat hepatocytes. Hepatology 28: 286–295

    Article  PubMed  CAS  Google Scholar 

  18. Kutty RK, Daniel RF, Ryan DE, Levin W, Maines MD (1988) Rat liver cytochrome P-450b, P-420b, and P-420c are degraded to biliverdin by heme oxygenase. Arch Biochem Biophys 260: 638–644

    Article  PubMed  CAS  Google Scholar 

  19. Wakabayashi Y, Takamiya R, Mizuki A, Goda N, Yamaguchi T, Takeoka S, Tsuchida E, Suematsu M, Ishimura Y (1999) Carbon monoxide overproduced by heme oxygenase1 causes a reduction of vascular resistance in perfused rat liver. Am J Physiol Gastrointest Liver Physiol 277: G1088 - G1096

    CAS  Google Scholar 

  20. Kyokane T, Norimizu S, Taniai H, Yamaguchi T, Takeoka S, Tsuchida E, Naito M, Nimura Y, Ishimura Y, Suematsu M (2001) Carbon monoxide from heme catabolism protects against hepatobiliary dysfunction in endotoxin-treated rat liver. Gastroenterology 120: 1227–1240

    Article  PubMed  CAS  Google Scholar 

  21. Yang L, Quan S, Abraham NG (1999) Retrovirus-mediated HO gene transfer into endothelial cells protects against oxidant-induced injury. Am J Physiol 277: L127 - L133

    PubMed  CAS  Google Scholar 

  22. Hayashi S, Takamiya R, Makino N, Tamatani T, Yamaguchi T, Tojo SJ, Ishimura Y, Suematsu M (1999) Induction of heme oxygenase-1 attenuates oxidative stress-induced leukocyte adhesion: roles of bilirubin generated by the enzyme. Circ Res 85: 663–671

    Article  PubMed  CAS  Google Scholar 

  23. Ishikawa K, Navab M, Leitinger N, Fogelman AM, Lusis AJ (1997) Induction of heme oxygenase-1 inhibits the monocyte transmigration induced by mildly oxidized LDL. J Clin Invest 100: 1209–1216

    Article  PubMed  CAS  Google Scholar 

  24. Yachie A, Niida Y, Wada T (1999) Oxidative stress causes enhanced vascular endothelial cell injury in human heme oxygenase-1 deficiency. J Clin Invest 103: 126–135

    Article  Google Scholar 

  25. Ozawa N, Goda N, Makino N, Yamaguchi T, Yoshimura Y, Suematsu M (2002) Leydig cell-derived heme oxygenase-1 regulates apoptosis of premeiotic germ cells in response to stress. J Clin Invest 109: 457–467

    PubMed  CAS  Google Scholar 

  26. Hori R, Kashiba M, Toma T, Yachie A, Goda N, Makino N, Soejima A, Nagasawa T, Nakabayashi K, Suematsu M (2002) Gene transfection of H25A mutant heme oxygenase-1 protects cells against hydroperoxide-induced cytotoxicity. J Biol Chem 277: 10712–10718

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Integrative Medical Biology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-Ku, Tokyo, 160-8582, Japan

    Makoto Suematsu & Satoshi Kashiwagi

Authors
  1. Makoto Suematsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Satoshi Kashiwagi
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Gastroenterology and Hepatology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, 755-8505, Ube, Yamaguchi, Japan

    Kiwamu Okita M.D., Ph.D. (Professor and Chairman) (Professor and Chairman)

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Japan

About this paper

Cite this paper

Suematsu, M., Kashiwagi, S. (2003). Carbon Monoxide as a Gaseous Regulator of Liver Microcirculation. In: Okita, K. (eds) HCV/Oxidative Stress and Liver Disease. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67005-6_10

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-67005-6_10

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-67007-0

  • Online ISBN: 978-4-431-67005-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation