Conditional expression of 15-lipoxygenase-1 inhibits the selenoenzyme thioredoxin reductase. Modulation of selenoproteins by lipoxygenase enzymes
Margaret K. Yu, Philip J. Moos, Pamela Cassidy, Mark Wade, F. A. Fitzpatrick
The selenoenzyme thioredoxin reductase regulates redox-sensitive proteins involved in inflammation and carcinogenesis, including ribonucleotide reductase, p55, NFκB, and others. Little is known about endogenous cellular factors that modulate thioredoxin reductase activity. Here we report that several metabolites of 15-lipoxygenase-1 inhibit purified thioredoxin reductase in vitro. 15(S)-Hydroperoxy-5,8,11-cis-15-trans-eico-satetraenoic acid, a metastable hydroperoxide generated by 15-lipoxygenase-1, and 4-hydroxy-2-nonenal, its non-enzymatic rearrangement product inhibit thioredoxin reductase with IC50 = 13 ± 1.5 μM and 1 ± 0.2 μM, respectively. Endogenously generated metabolites of 15-lipoxygenase-1 also inhibit thioredoxin reductase in HEK-293 cells that harbor a 15-LOX-1 gene under the control of an inducible promoter complex. Conditional, highly selective induction of 15-lipoxygenase-1 caused an inhibition of ribonucleotide reductase activity, cell cycle arrest in G1, impairment of anchorage-independent growth, and accumulation of the pro-apoptotic protein BAX. All of these responses are consistent with inhibition of thioredoxin reductase via 15-lipoxygenase-1 overexpression. In contrast, metabolites of 5-lipoxygenase were poor inhibitors of isolated thioredoxin reductase, and the overexpression of 5-lipoxygenase did not inhibit thioredoxin reductase or cause a G1 cell cycle arrest. The influences of 15-lipoxygenase-1 on inflammation, cell growth, and survival may be attributable, in part, to inhibition of thioredoxin reductase and several redox-sensitive processes subordinate to thioredoxin reductase.
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Arachidonate 15-Lipoxygenase Chemical Compounds
Thioredoxin-Disulfide Reductase Chemical Compounds
Selenoproteins Chemical Compounds
Lipoxygenase Chemical Compounds
Modulation Chemical Compounds
Metabolites Chemical Compounds
Ribonucleotide Reductases Chemical Compounds
Yu, M. K., Moos, P. J., Cassidy, P., Wade, M., & Fitzpatrick, F. A. (2004). Conditional expression of 15-lipoxygenase-1 inhibits the selenoenzyme thioredoxin reductase. Modulation of selenoproteins by lipoxygenase enzymes. Journal of Biological Chemistry, 279(27), 28028-28035. https://doi.org/10.1074/jbc.M313939200
Conditional expression of 15-lipoxygenase-1 inhibits the selenoenzyme thioredoxin reductase. Modulation of selenoproteins by lipoxygenase enzymes. / Yu, Margaret K.; Moos, Philip J.; Cassidy, Pamela; Wade, Mark; Fitzpatrick, F. A.
Yu, MK, Moos, PJ, Cassidy, P, Wade, M & Fitzpatrick, FA 2004, 'Conditional expression of 15-lipoxygenase-1 inhibits the selenoenzyme thioredoxin reductase. Modulation of selenoproteins by lipoxygenase enzymes', Journal of Biological Chemistry, vol. 279, no. 27, pp. 28028-28035. https://doi.org/10.1074/jbc.M313939200
Yu MK, Moos PJ, Cassidy P, Wade M, Fitzpatrick FA. Conditional expression of 15-lipoxygenase-1 inhibits the selenoenzyme thioredoxin reductase. Modulation of selenoproteins by lipoxygenase enzymes. Journal of Biological Chemistry. 2004 Jul 2;279(27):28028-28035. https://doi.org/10.1074/jbc.M313939200
Yu, Margaret K. ; Moos, Philip J. ; Cassidy, Pamela ; Wade, Mark ; Fitzpatrick, F. A. / Conditional expression of 15-lipoxygenase-1 inhibits the selenoenzyme thioredoxin reductase. Modulation of selenoproteins by lipoxygenase enzymes. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 27. pp. 28028-28035.
@article{d6ddcec87fe14fc3bae508469e5f02c8,
title = "Conditional expression of 15-lipoxygenase-1 inhibits the selenoenzyme thioredoxin reductase. Modulation of selenoproteins by lipoxygenase enzymes",
abstract = "The selenoenzyme thioredoxin reductase regulates redox-sensitive proteins involved in inflammation and carcinogenesis, including ribonucleotide reductase, p55, NFκB, and others. Little is known about endogenous cellular factors that modulate thioredoxin reductase activity. Here we report that several metabolites of 15-lipoxygenase-1 inhibit purified thioredoxin reductase in vitro. 15(S)-Hydroperoxy-5,8,11-cis-15-trans-eico-satetraenoic acid, a metastable hydroperoxide generated by 15-lipoxygenase-1, and 4-hydroxy-2-nonenal, its non-enzymatic rearrangement product inhibit thioredoxin reductase with IC50 = 13 ± 1.5 μM and 1 ± 0.2 μM, respectively. Endogenously generated metabolites of 15-lipoxygenase-1 also inhibit thioredoxin reductase in HEK-293 cells that harbor a 15-LOX-1 gene under the control of an inducible promoter complex. Conditional, highly selective induction of 15-lipoxygenase-1 caused an inhibition of ribonucleotide reductase activity, cell cycle arrest in G1, impairment of anchorage-independent growth, and accumulation of the pro-apoptotic protein BAX. All of these responses are consistent with inhibition of thioredoxin reductase via 15-lipoxygenase-1 overexpression. In contrast, metabolites of 5-lipoxygenase were poor inhibitors of isolated thioredoxin reductase, and the overexpression of 5-lipoxygenase did not inhibit thioredoxin reductase or cause a G1 cell cycle arrest. The influences of 15-lipoxygenase-1 on inflammation, cell growth, and survival may be attributable, in part, to inhibition of thioredoxin reductase and several redox-sensitive processes subordinate to thioredoxin reductase.",
author = "Yu, {Margaret K.} and Moos, {Philip J.} and Pamela Cassidy and Mark Wade and Fitzpatrick, {F. A.}",
T1 - Conditional expression of 15-lipoxygenase-1 inhibits the selenoenzyme thioredoxin reductase. Modulation of selenoproteins by lipoxygenase enzymes
AU - Yu, Margaret K.
AU - Moos, Philip J.
AU - Cassidy, Pamela
AU - Wade, Mark
AU - Fitzpatrick, F. A.
N2 - The selenoenzyme thioredoxin reductase regulates redox-sensitive proteins involved in inflammation and carcinogenesis, including ribonucleotide reductase, p55, NFκB, and others. Little is known about endogenous cellular factors that modulate thioredoxin reductase activity. Here we report that several metabolites of 15-lipoxygenase-1 inhibit purified thioredoxin reductase in vitro. 15(S)-Hydroperoxy-5,8,11-cis-15-trans-eico-satetraenoic acid, a metastable hydroperoxide generated by 15-lipoxygenase-1, and 4-hydroxy-2-nonenal, its non-enzymatic rearrangement product inhibit thioredoxin reductase with IC50 = 13 ± 1.5 μM and 1 ± 0.2 μM, respectively. Endogenously generated metabolites of 15-lipoxygenase-1 also inhibit thioredoxin reductase in HEK-293 cells that harbor a 15-LOX-1 gene under the control of an inducible promoter complex. Conditional, highly selective induction of 15-lipoxygenase-1 caused an inhibition of ribonucleotide reductase activity, cell cycle arrest in G1, impairment of anchorage-independent growth, and accumulation of the pro-apoptotic protein BAX. All of these responses are consistent with inhibition of thioredoxin reductase via 15-lipoxygenase-1 overexpression. In contrast, metabolites of 5-lipoxygenase were poor inhibitors of isolated thioredoxin reductase, and the overexpression of 5-lipoxygenase did not inhibit thioredoxin reductase or cause a G1 cell cycle arrest. The influences of 15-lipoxygenase-1 on inflammation, cell growth, and survival may be attributable, in part, to inhibition of thioredoxin reductase and several redox-sensitive processes subordinate to thioredoxin reductase.
AB - The selenoenzyme thioredoxin reductase regulates redox-sensitive proteins involved in inflammation and carcinogenesis, including ribonucleotide reductase, p55, NFκB, and others. Little is known about endogenous cellular factors that modulate thioredoxin reductase activity. Here we report that several metabolites of 15-lipoxygenase-1 inhibit purified thioredoxin reductase in vitro. 15(S)-Hydroperoxy-5,8,11-cis-15-trans-eico-satetraenoic acid, a metastable hydroperoxide generated by 15-lipoxygenase-1, and 4-hydroxy-2-nonenal, its non-enzymatic rearrangement product inhibit thioredoxin reductase with IC50 = 13 ± 1.5 μM and 1 ± 0.2 μM, respectively. Endogenously generated metabolites of 15-lipoxygenase-1 also inhibit thioredoxin reductase in HEK-293 cells that harbor a 15-LOX-1 gene under the control of an inducible promoter complex. Conditional, highly selective induction of 15-lipoxygenase-1 caused an inhibition of ribonucleotide reductase activity, cell cycle arrest in G1, impairment of anchorage-independent growth, and accumulation of the pro-apoptotic protein BAX. All of these responses are consistent with inhibition of thioredoxin reductase via 15-lipoxygenase-1 overexpression. In contrast, metabolites of 5-lipoxygenase were poor inhibitors of isolated thioredoxin reductase, and the overexpression of 5-lipoxygenase did not inhibit thioredoxin reductase or cause a G1 cell cycle arrest. The influences of 15-lipoxygenase-1 on inflammation, cell growth, and survival may be attributable, in part, to inhibition of thioredoxin reductase and several redox-sensitive processes subordinate to thioredoxin reductase.