Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation

Nobuhito Goda, Kensuke Suzuki, Makoto Naito, Shinji Takeoka, Eishun Tsuchida, Yuzuru Ishimura, Takuya Tamatani, Makoto Suematsu

Research output: Contribution to journalArticle

238 Citations (Scopus)

Abstract

Carbon monoxide (CO) derived from heme oxygenase has recently been shown to play a role in controlling hepatobiliary function, but intrahepatic distribution of the enzyme is unknown. We examined distribution of two kinds of the heme oxygenase isoforms (HO-1 and HO-2) in rat liver immunohistochemically using monoclonal antibodies. The results showed that distribution of the two isoforms had distinct topographic patterns: HO-1, an inducible isoform, was observed only in Kupffer cells, while HO-2, a constitutive form, distributed to parenchymal cells, but not to Kupffer cells. Both isoforms were undetectable in hepatic stellate cells and sinusoidal endothelial cells. Of the two isoforms, HO-2 in the parenchymal cell rather than HO-1 in the Kupffer cell, appears to play a major role in regulation of microvascular tone. In the perfused liver, administration of HbO2, a CO-trapping reagent that can diffuse across the fenestrated endothelium into the space of Disse, elicited a marked sinusoidal constriction, while administration of a liposome-encapsulated Hb that cannot enter the space had no effect on the microvascular tone. These results suggest that CO evolved by HO-2 in the parenchymal cells, and, released to the extrasinusoidal space, served as the physiological relaxant for hepatic sinusoids.

Original languageEnglish
Pages (from-to)604-612
Number of pages9
JournalJournal of Clinical Investigation
Volume101
Issue number3
Publication statusPublished - 1998 Feb 1

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Heme Oxygenase (Decyclizing)
Carbon Monoxide
Protein Isoforms
Kupffer Cells
Liver
Hepatic Stellate Cells
Constriction
Liposomes
Endothelium
Endothelial Cells
Monoclonal Antibodies
Enzymes

Keywords

  • Heme oxygenase-1
  • Heme oxygenase-2
  • Hemoglobin
  • Hepatic stellate cells
  • Kupffer cells

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Goda, N., Suzuki, K., Naito, M., Takeoka, S., Tsuchida, E., Ishimura, Y., ... Suematsu, M. (1998). Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation. Journal of Clinical Investigation, 101(3), 604-612.

Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation. / Goda, Nobuhito; Suzuki, Kensuke; Naito, Makoto; Takeoka, Shinji; Tsuchida, Eishun; Ishimura, Yuzuru; Tamatani, Takuya; Suematsu, Makoto.

In: Journal of Clinical Investigation, Vol. 101, No. 3, 01.02.1998, p. 604-612.

Research output: Contribution to journalArticle

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', Journal of Clinical Investigation, vol. 101, no. 3, pp. 604-612.
Goda, Nobuhito ; Suzuki, Kensuke ; Naito, Makoto ; Takeoka, Shinji ; Tsuchida, Eishun ; Ishimura, Yuzuru ; Tamatani, Takuya ; Suematsu, Makoto. / Distribution of heme oxygenase isoforms in rat liver. Topographic basis for carbon monoxide-mediated microvascular relaxation. In: Journal of Clinical Investigation. 1998 ; Vol. 101, No. 3. pp. 604-612.
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