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Oxidant-mediated modification of the cellular thiols is sufficient for arginase activation in cultured cells

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Abstract

Increased arginase activity in the vasculature has been implicated in the regulation of nitric oxide (NO) homeostasis, leading to the development of vascular disease and the promotion of tumor cell growth. Recently, we showed that cysteine, in the presence of iron, promotes arginase activity by driving the Fenton reaction. In the present report, we showed that induction of oxidative stress in erythroleukemic cells with the thiol-specific oxidant, diamide, led to an increase in arginase activity by 42% (P = 0.02; vs. control). By using specific antibodies, it was demonstrated that this increase correlated with an increase in arginase-1 levels in the cells and with corresponding decreases in glutathione and protein thiol levels. Treatment of cells with aurothiomalate (ATM), a protein thiol-complexing agent, diminished the activity of arginase and arginase-1 levels by 19.5 and 35.2%, respectively (vs. control) and significantly decreased both glutathione and protein thiol levels, further implicating the thiol redox system in the cellular activation of arginase. Furthermore, diamide significantly altered the kinetics of arginase, resulting in the doubling of its V max (vs. control). Our presented data demonstrate, for the first time that the intracellular arginase activation is may be enhanced in part, via a cellular thiol-mediated mechanism.

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Acknowledgments

We wish to thank Dr. Tarak Srivastava for the illuminating discussions. This study was supported in part by Grant KO1 HL076695-01 from the National Institutes of Health.

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Authors and Affiliations

  1. Division of Hematology and Oncology, Children’s Mercy Hospital, Kansas City, MO, 64108, USA

    Efemwonkiekie W. Iyamu, Harrison A. Perdew & Gerald M. Woods

  2. Department of Pediatrics, University of Missouri Medical Center, Kansas City, MO, 64108, USA

    Efemwonkiekie W. Iyamu & Gerald M. Woods

  3. Department of Internal Medicine, Meharry Medical College, 1005 DB Todd BLVD, Nashville, TN, 37208, USA

    Efemwonkiekie W. Iyamu

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  1. Efemwonkiekie W. Iyamu
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  2. Harrison A. Perdew
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Correspondence to Efemwonkiekie W. Iyamu.

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Iyamu, E.W., Perdew, H.A. & Woods, G.M. Oxidant-mediated modification of the cellular thiols is sufficient for arginase activation in cultured cells. Mol Cell Biochem 360, 159–168 (2012). https://doi.org/10.1007/s11010-011-1053-5

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