TY - JOUR T1 - Roles of Heme Oxygenase-1 in the Antiproliferative and Antiapoptotic Effects of Nitric Oxide on Jurkat T Cells JF - Molecular Pharmacology JO - Mol Pharmacol SP - 122 LP - 128 DO - 10.1124/mol.66.1.122 VL - 66 IS - 1 AU - Hyun-Ock Pae AU - Byung-Min Choi AU - Gi-Su Oh AU - Myeong-Su Lee AU - Do-Gon Ryu AU - Hyun-Yul Rhew AU - Yung-Myung Kim AU - Hun-Taeg Chung Y1 - 2004/07/01 UR - http://molpharm.aspetjournals.org/content/66/1/122.abstract N2 - 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. ER -