Biomaterial Database

Copper egress is induced by PMA in human THP-1 monocytic cell line. 2009

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

Division of Cardiovascular Disease, College of Medicine, University of Cincinnati, 231 Albert Sabin Way, Mail Location 0542, Cincinnati, OH 45267, USA.

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.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000073840	Copper-Transporting ATPases	P-type ATPases which transport copper ions across membranes in prokaryotic and eukaryotic cells. They possess a conserved CYSTEINE-HISTIDINE-SERINE (CPx) amino acid motif within their transmembrane helices that functions in cation translocation and catalytic activation, and an N-terminal copper-binding CxxC motif that regulates enzyme activity. They play essential roles in intracellular copper homeostasis through regulating the uptake, efflux and storage of copper ions, and in cuproprotein biosynthesis.	ATP7B Cu-Binding P Type ATPase,ATPase, Cu++ Transporting, beta Polypeptide (Wilson Disease),Copper-Transporting ATPase,Copper-Transporting ATPase 1,Copper-Transporting ATPase 2,Copper-Transporting Adenosine Triphosphatases,Cu(+)-Transporting ATPases,Cu-Transporting ATPases,Menkes Disease-Associated Protein,Pineal Night-Specific ATPase,Wilson Disease Cu-Binding P Type ATPase,ATP7A Protein,ATPase Copper Transporting alpha,Copper Pump 1,PINA Enzyme,Wilson Disease Protein,ATP7B Cu Binding P Type ATPase,ATPase 1, Copper-Transporting,ATPase 2, Copper-Transporting,ATPase, Copper-Transporting,ATPase, Pineal Night-Specific,ATPases, Copper-Transporting,ATPases, Cu-Transporting,Adenosine Triphosphatases, Copper-Transporting,Copper Transporting ATPase,Copper Transporting ATPase 1,Copper Transporting ATPase 2,Copper Transporting ATPases,Copper Transporting Adenosine Triphosphatases,Cu Transporting ATPases,Menkes Disease Associated Protein,Night-Specific ATPase, Pineal,Pineal Night Specific ATPase,Triphosphatases, Copper-Transporting Adenosine,Wilson Disease Cu Binding P Type ATPase
D000251	Adenosine Triphosphatases	A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.	ATPases,Adenosinetriphosphatase,ATPase,ATPase, DNA-Dependent,Adenosine Triphosphatase,DNA-Dependent ATPase,DNA-Dependent Adenosinetriphosphatases,ATPase, DNA Dependent,Adenosinetriphosphatases, DNA-Dependent,DNA Dependent ATPase,DNA Dependent Adenosinetriphosphatases,Triphosphatase, Adenosine
D013755	Tetradecanoylphorbol Acetate	A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.	Phorbol Myristate Acetate,12-Myristoyl-13-acetylphorbol,12-O-Tetradecanoyl Phorbol 13-Acetate,Tetradecanoylphorbol Acetate, 4a alpha-Isomer,12 Myristoyl 13 acetylphorbol,12 O Tetradecanoyl Phorbol 13 Acetate,13-Acetate, 12-O-Tetradecanoyl Phorbol,Acetate, Phorbol Myristate,Acetate, Tetradecanoylphorbol,Myristate Acetate, Phorbol,Phorbol 13-Acetate, 12-O-Tetradecanoyl,Tetradecanoylphorbol Acetate, 4a alpha Isomer
D015870	Gene Expression	The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.	Expression, Gene,Expressions, Gene,Gene Expressions
D017136	Ion Transport	The movement of ions across energy-transducing cell membranes. Transport can be active, passive or facilitated. Ions may travel by themselves (uniport), or as a group of two or more ions in the same (symport) or opposite (antiport) directions.	Antiport,Ion Cotransport,Ion Exchange, Intracellular,Symport,Uniport,Active Ion Transport,Facilitated Ion Transport,Passive Ion Transport,Cotransport, Ion,Exchange, Intracellular Ion,Intracellular Ion Exchange,Ion Transport, Active,Ion Transport, Facilitated,Ion Transport, Passive,Transport, Active Ion,Transport, Ion
D020133	Reverse Transcriptase Polymerase Chain Reaction	A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.	Polymerase Chain Reaction, Reverse Transcriptase,Reverse Transcriptase PCR,PCR, Reverse Transcriptase,Transcriptase PCR, Reverse