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 language | English (US) |
|---|---|
| Pages (from-to) | 531-539 |
| Number of pages | 9 |
| Journal | BioMetals |
| Volume | 22 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jun 2009 |
| Externally published | Yes |
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Keywords
- ATP7A
- Copper
ASJC Scopus subject areas
- Biomaterials
- Metals and Alloys
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
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, 06.2009, p. 531-539.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Copper egress is induced by PMA in human THP-1 monocytic cell line
AU - Afton, Scott E.
AU - Caruso, Joseph A.
AU - Britigan, Bradley E.
AU - Qin, Zhenyu
PY - 2009/6
Y1 - 2009/6
N2 - 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.
AB - 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.
KW - ATP7A
KW - Copper
UR - http://www.scopus.com/inward/record.url?scp=67349180198&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67349180198&partnerID=8YFLogxK
U2 - 10.1007/s10534-009-9210-y
DO - 10.1007/s10534-009-9210-y
M3 - Article
C2 - 19205902
AN - SCOPUS:67349180198
VL - 22
SP - 531
EP - 539
JO - BioMetals
JF - BioMetals
SN - 0966-0844
IS - 3
ER -