Copper egress is induced by PMA in human THP-1 monocytic cell line

Scott E. Afton, Joseph A. Caruso, Bradley E. Britigan, Zhenyu Qin

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Copper egress is an essential regulator of the kinetics of cellular copper and is primarily regulated by ATP7A, a copper-transporting P-type ATPase. However, little is known under which physiological condition copper egress is induced and its molecular consequence. In current manuscript, using THP-1 cells, a human monocytic cell line, we found that ATP7A expression was increased in cells exposed to phorbol-12-myristate-13-acetate (PMA), a potent inducer of neovascularization and cancer. Inductively coupled plasma mass spectrometry revealed that PMA also induced copper egress. Inhibition of ATP7A expression using small interfering RNA abrogated PMA induced copper egress. PMA treatment in THP-1 cells resulted in increased expression of matrix metalloproteinase (MMP) 9 and vascular endothelial growth factor receptor 1 (VEGFR1), whereas inhibition of ATP7A resulted in suppression of PMA-induced expression of VEGFR1, but not MMP9. Finally, addition of exogenous copper into the conditioned medium did not change VEGFR1 expression in THP-1 cells. Collectively, we demonstrate that PMA induces copper egress in THP-1 cells, which is regulated by ATP7A, and ATP7A regulates VEGFR1 expression. Considering the involvement of copper in neovascularization, our current finding provides the potential evidence to interpret the molecular mechanism.

Original languageEnglish (US)
Pages (from-to)531-539
Number of pages9
JournalBioMetals
Volume22
Issue number3
DOIs
StatePublished - Jun 1 2009

Fingerprint

Copper
Acetates
copper
acetates
Cells
cell lines
vascular endothelial growth factor receptor-1
Vascular Endothelial Growth Factor Receptor-1
Cell Line
angiogenesis
cells
Manuscripts
phorbol-12-myristate
Inductively coupled plasma mass spectrometry
Matrix Metalloproteinase 9
gelatinase B
Conditioned Culture Medium
atomic absorption spectrometry
Small Interfering RNA
small interfering RNA

Keywords

  • ATP7A
  • Copper

ASJC Scopus subject areas

  • Biomaterials
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Metals and Alloys

Cite this

Copper egress is induced by PMA in human THP-1 monocytic cell line. / Afton, Scott E.; Caruso, Joseph A.; Britigan, Bradley E.; Qin, Zhenyu.

In: BioMetals, Vol. 22, No. 3, 01.06.2009, p. 531-539.

Research output: Contribution to journalArticle

Afton, Scott E. ; Caruso, Joseph A. ; Britigan, Bradley E. ; Qin, Zhenyu. / Copper egress is induced by PMA in human THP-1 monocytic cell line. In: BioMetals. 2009 ; Vol. 22, No. 3. pp. 531-539.
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