The physiological concentration of ferrous iron (II) alters the inhibitory effect of hydrogen peroxide on CD45, LAR and PTP1B phosphatases.

Alicja Kuban-Jankowska,Jack A Tuszynski,Michal Wozniak,Magdalena Gorska,Mariusz Jaremko,Lukasz Jaremko

doi:10.1007/s10534-015-9882-4

Abstract

Hydrogen peroxide is an important regulator of protein tyrosine phosphatase activity via reversible oxidation. However, the role of iron in this reaction has not been yet elucidated. Here we compare the influence of hydrogen peroxide and the ferrous iron (reagent for Fenton reaction) on the enzymatic activity of recombinant CD45, LAR, PTP1B phosphatases and cellular CD45 in Jurkat cells. The obtained results show that ferrous iron (II) is potent inhibitor of CD45, LAR and PTP1B, but the inhibitory effect is concentration dependent. We found that the higher concentrations of ferrous iron (II) increase the inactivation of CD45, LAR and PTP1B phosphatase caused by hydrogen peroxide, but the addition of the physiological concentration (500 nM) of ferrous iron (II) has even a slightly preventive effect on the phosphatase activity against hydrogen peroxide.

Highlights

Protein tyrosine phosphatases (PTPs) are responsible for the regulation of tyrosine phosphorylation status controlling numerous cellular processes, such as cellular growth, differentiation, metabolism, cell–cell communication and immune response (Tonks 2006)
To asses the effect of ferrous iron (II) and hydrogen peroxide we measured the enzymatic activity of recombinant CD45, LAR and PTP1B phosphatases under the cell-free conditions and CD45 phosphatase in Jurkat cells
We compared the effect of hydrogen peroxide with ferrous iron (II) and we found that hydrogen peroxide induces inactivation of recombinant CD45 more effectively than in the presence of physiological concentration of ferrous iron (II)

Summary

Introduction

Protein tyrosine phosphatases (PTPs) are responsible for the regulation of tyrosine phosphorylation status controlling numerous cellular processes, such as cellular growth, differentiation, metabolism, cell–cell communication and immune response (Tonks 2006). Phosphatases PTP1B is involved in pathogenesis of type 2 diabetes and obesity (Bence et al 2006) and is a target in breast cancer treatment (Aceto and Bentires-Alj 2012). LAR phosphatase have been implicated in metabolic regulation and cancer (Chagnon et al 2004). CD45 and LAR are receptor-like PTPs predominantly found in the plasma membrane, while PTP1B is intracellular (cytosolic) phosphatase localized in a variety of intracellular compartments, such as cytosol, plasma membrane or endoplasmic reticulum (Andersen et al 2001)

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