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

Biometals. 2015 Dec;28(6):975-86. doi: 10.1007/s10534-015-9882-4. Epub 2015 Sep 25.

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.

Keywords: CD45; Ferrous iron; Hydrogen peroxide; LAR; PTP1B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Ferrous Compounds / pharmacology*
  • Gene Expression Regulation
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Jurkat Cells
  • Leukocyte Common Antigens / antagonists & inhibitors
  • Leukocyte Common Antigens / genetics*
  • Leukocyte Common Antigens / metabolism
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / genetics*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / antagonists & inhibitors
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / genetics*
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2 / metabolism
  • Signal Transduction

Substances

  • Ferrous Compounds
  • ferrous sulfate
  • Hydrogen Peroxide
  • Leukocyte Common Antigens
  • PTPN1 protein, human
  • PTPRC protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Receptor-Like Protein Tyrosine Phosphatases, Class 2