Molecular and Cellular Biochemistry

, Volume 360, Issue 1, pp 159–168

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

  • Efemwonkiekie W. Iyamu
  • Harrison A. Perdew
  • Gerald M. Woods
Article

DOI: 10.1007/s11010-011-1053-5

Cite this article as:
Iyamu, E.W., Perdew, H.A. & Woods, G.M. Mol Cell Biochem (2012) 360: 159. doi:10.1007/s11010-011-1053-5

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 Vmax (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.

Keywords

Arginase activationGlutathioneProtein thiolsSulfhydryl group oxidationEnzyme kinetics

Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Efemwonkiekie W. Iyamu
    • 1
    • 2
    • 3
  • Harrison A. Perdew
    • 1
  • Gerald M. Woods
    • 1
    • 2
  1. 1.Division of Hematology and OncologyChildren’s Mercy HospitalKansas CityUSA
  2. 2.Department of PediatricsUniversity of Missouri Medical CenterKansas CityUSA
  3. 3.Department of Internal MedicineMeharry Medical CollegeNashvilleUSA