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Molecular Pharmacology

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Research ArticleArticle

Roles of Heme Oxygenase-1 in the Antiproliferative and Antiapoptotic Effects of Nitric Oxide on Jurkat T Cells

Hyun-Ock Pae, Byung-Min Choi, Gi-Su Oh, Myeong-Su Lee, Do-Gon Ryu, Hyun-Yul Rhew, Yung-Myung Kim and Hun-Taeg Chung
Molecular Pharmacology July 2004, 66 (1) 122-128; DOI: https://doi.org/10.1124/mol.66.1.122
Hyun-Ock Pae
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Byung-Min Choi
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Gi-Su Oh
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Myeong-Su Lee
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Do-Gon Ryu
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Hyun-Yul Rhew
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Yung-Myung Kim
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Hun-Taeg Chung
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Abstract

Nitric oxide (NO) has been shown to exert antiproliferative and antiapoptotic effects on human T cells. Heme oxygenase-1 (HO-1), which degrades heme into biliverdin, free iron (Fe2+), and carbon monoxide (CO), has also been known to have antiproliferative and antiapoptotic effects. Recent evidence suggests that HO-1 is an important cellular target of NO; whether HO-1 expression contributes to the antiproliferative and/or antiapoptotic effects mediated by NO remains to be investigated. In the present study, we examined the effects of NO on HO-1 expression and possible roles of HO-1 in T cell proliferation and apoptosis. Using human Jurkat T cells, we found that the NO donor sodium nitroprusside (SNP) induced HO-1 expression and that preincubation with SNP suppressed T cell proliferation induced by concanavalin A and apoptosis triggered by anti-Fas antibody. Suppressions of T cell proliferation and apoptosis comparable with SNP were also observed when the T cells were preincubated with the HO-1 inducer cobalt protoporphyrin. A phosphorothioate-linked HO-1 antisense oligonucleotide blocked HO-1 expression, and subsequently abrogated the antiproliferative and antiapoptotic effects of SNP. Overexpression of the HO-1 gene after transfection into Jurkat T cells resulted in significant decreases in T cell proliferation and apoptosis. The CO donor tricarbonyldichlororuthenium (II) dimer mimicked the antiproliferative effect of SNP, and the Fe2+ donor FeSO4 blocked anti-Fas-induced apoptosis. Taken together, our results suggest that NO induces HO-1 expression in T cells and that suppressions of T cell proliferation and apoptosis afforded by NO are associated with an increased expression of HO-1 by NO.

  • Received January 22, 2004.
  • Accepted April 7, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 66 (1)
Molecular Pharmacology
Vol. 66, Issue 1
1 Jul 2004
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Research ArticleArticle

Roles of Heme Oxygenase-1 in the Antiproliferative and Antiapoptotic Effects of Nitric Oxide on Jurkat T Cells

Hyun-Ock Pae, Byung-Min Choi, Gi-Su Oh, Myeong-Su Lee, Do-Gon Ryu, Hyun-Yul Rhew, Yung-Myung Kim and Hun-Taeg Chung
Molecular Pharmacology July 1, 2004, 66 (1) 122-128; DOI: https://doi.org/10.1124/mol.66.1.122

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Research ArticleArticle

Roles of Heme Oxygenase-1 in the Antiproliferative and Antiapoptotic Effects of Nitric Oxide on Jurkat T Cells

Hyun-Ock Pae, Byung-Min Choi, Gi-Su Oh, Myeong-Su Lee, Do-Gon Ryu, Hyun-Yul Rhew, Yung-Myung Kim and Hun-Taeg Chung
Molecular Pharmacology July 1, 2004, 66 (1) 122-128; DOI: https://doi.org/10.1124/mol.66.1.122
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