Glutathione S-Transferase P influences redox and migration pathways in bone marrow

Jie Zhang, Zhi Wei Ye, Peng Gao, Leticia Reyes, Elizabeth E. Jones, Melissa Branham-O'Connor, Joe B. Blumer, Richard R. Drake, Yefim Manevich, Danyelle M. Townsend, Kenneth D. Tew

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

To interrogate why redox homeostasis and glutathione S-transferase P (GSTP) are important in regulating bone marrow cell proliferation and migration, we isolated crude bone marrow, lineage negative and bone marrow derived-dendritic cells (BMDDCs) from both wild type (WT) and knockout (Gstp1/p2-/-) mice. Comparison of the two strains showed distinct thiol expression patterns. WT had higher baseline and reactive oxygen species-induced levels of S-glutathionylated proteins, some of which (sarco-endoplasmic reticulum Ca2+-ATPase) regulate Ca2+ fluxes and subsequently influence proliferation and migration. Redox status is also a crucial determinant in the regulation of the chemokine system. CXCL12 chemotactic response was stronger in WT cells, with commensurate alterations in plasma membrane polarization/permeability and intracellular calcium fluxes; activities of the downstream kinases, ERK and Akt were also higher in WT. In addition, expression levels of the chemokine receptor CXCR4 and its associated phosphatase, SHP-2, were higher in WT. Inhibition of CXCR4 or SHP2 decreased the extent of CXCL12-induced migration in WT BMDDCs. The differential surface densities of CXCR4, SHP-2 and inositol trisphosphate receptor in WT and Gstp1/p2-/-cells correlated with the differential CXCR4 functional activities, as measured by the extent of chemokine-induced directional migration and differences in intracellular signaling. These observed differences contribute to our understanding of how genetic ablation of GSTP causes higher levels of myeloproliferation and migration.

Original languageEnglish (US)
Article numbere0107478
JournalPloS one
Volume9
Issue number9
DOIs
StatePublished - Sep 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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