title: CTR1 silencing inhibits angiogenesis by limiting copper entry into endothelial cells.
abstract: Increased levels of intracellular copper stimulate angiogenesis in human umbilical vein endothelial cells (HUVECs). Copper transporter 1 (CTR1) is a copper importer present in the cell membrane and plays a major role in copper transport. In this study, three siRNAs targeting CTR1 mRNA were designed and screened for gene silencing. HUVECs when exposed to 100 µM copper showed 3 fold increased proliferation, migration by 1.8-fold and tube formation by 1.8-fold. One of the designed CTR1 siRNA (si 1) at 10 nM concentration decreased proliferation by 2.5-fold, migration by 4-fold and tube formation by 2.8-fold. Rabbit corneal packet assay also showed considerable decrease in matrigel induced blood vessel formation by si 1 when compared to untreated control. The designed si 1 when topically applied inhibited angiogenesis. This can be further developed for therapeutic application.
authors.affiliation: R. S. Mehta Jain Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, India ; Birla Institute of Technology and Science, Pilani (Rajasthan), India.
authors.forename: Gomathy
authors.initials: G
authors.lastname: Narayanan
authors.forename: Bharathidevi S
authors.initials: BS
authors.lastname: R
authors.forename: Harish
authors.initials: H
authors.lastname: Vuyyuru
authors.forename: Bharathselvi
authors.initials: B
authors.lastname: Muthuvel
authors.forename: Sulochana
authors.initials: S
authors.lastname: Konerirajapuram Natrajan
mesh_terms: D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D005260:Female; D055785:Gene Knockdown Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic; D034741:RNA, Small Interfering / Q000235:genetics; D011817:Rabbits; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D034741:RNA, Small Interfering; C490079:SLC31A1 protein, human; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003300:Copper
references.citation: Ann Surg. 1972 Mar;175(3):409-16
references.pmid: 5077799
references.citation: Nutr Rev. 2004 Feb;62(2):60-4
references.pmid: 15080367
references.citation: J Natl Cancer Inst. 2012 Jan 18;104(2):93-113
references.pmid: 22235142
references.citation: Chem Rev. 2009 Oct;109(10):4760-79
references.pmid: 19824702
references.citation: Neuro Oncol. 2005 Jul;7(3):246-53
references.pmid: 16053699
references.citation: Trans Ophthalmol Soc U K (1962). 1980 Sep;100(3):354-8
references.pmid: 6171067
references.citation: Nat Protoc. 2007;2(2):329-33
references.pmid: 17406593
references.citation: Eur J Hum Genet. 2010 May;18(5):511-8
references.pmid: 19888294
references.citation: J Exp Med. 2007 Mar 19;204(3):657-66
references.pmid: 17339407
references.citation: Indian J Med Res. 2008 Oct;128(4):448-61
references.pmid: 19106440
references.citation: Am J Physiol Cell Physiol. 2002 May;282(5):C947-70
references.pmid: 11940508
references.citation: J Biol Inorg Chem. 2010 Jan;15(1):47-59
references.pmid: 19851794
references.citation: Thromb Res. 2012 Apr;129 Suppl 1:S50-3
references.pmid: 22682133
references.citation: J Biol Chem. 2011 Sep 23;286(38):33167-77
references.pmid: 21795678
references.citation: J Mammary Gland Biol Neoplasia. 2005 Oct;10(4):299-310
references.pmid: 16924372
references.citation: Int J Biochem Cell Biol. 2003 Mar;35(3):288-91
references.pmid: 12531240
references.citation: Nat Biotechnol. 2004 Mar;22(3):326-30
references.pmid: 14758366
references.citation: Mol Pharmacol. 2009 Jan;75(1):174-82
references.pmid: 18842833
references.citation: J Trace Elem Med Biol. 2010 Jul;24(3):178-84
references.pmid: 20569931
references.citation: J Cell Biochem. 1998 Jun 1;69(3):326-35
references.pmid: 9581871
references.citation: J Biol Chem. 2002 Oct 25;277(43):40253-9
references.pmid: 12177073
references.citation: Am J Ophthalmol. 2010 Jul;150(1):33-39.e2
references.pmid: 20609706
references.citation: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references.pmid: 6606682
references.citation: Circ Res. 2010 Sep 17;107(6):787-99
references.pmid: 20671235
references.citation: Cell. 2002 Sep 6;110(5):563-74
references.pmid: 12230974
references.citation: J Pharmacol Exp Ther. 2012 Aug;342(2):561-7
references.pmid: 22619252
references.citation: Clin Cancer Res. 2007 Aug 1;13(15 Pt 2):s4623-7
references.pmid: 17671153
references.citation: Nature. 2005 Dec 15;438(7070):932-6
references.pmid: 16355210
references.citation: Cardiovasc Res. 2008 May 1;78(2):203-12
references.pmid: 18079100
references.citation: Nature. 2010 Apr 15;464(7291):1067-70
references.pmid: 20305636
references.citation: Nat Protoc. 2007;2(3):481-5
references.pmid: 17406610
references.citation: Anticancer Res. 2010 Sep;30(9):3249-55
references.pmid: 20944094
references.citation: Nucleic Acids Res. 2003 May 1;31(9):2401-7
references.pmid: 12711685
references.citation: Physiol Rev. 2007 Jul;87(3):1011-46
references.pmid: 17615395
references.citation: Clin Cancer Res. 2006 Aug 15;12(16):4974-82
references.pmid: 16914587
references.citation: Mol Vis. 2012;18:2454-67
references.pmid: 23077404
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: Am J Physiol Heart Circ Physiol. 2002 May;282(5):H1821-7
references.pmid: 11959648
references.citation: Gene Ther. 2005 Jan;12(1):5-11
references.pmid: 15496962
references.citation: Curr Biol. 2007 Feb 20;17(4):316-22
references.pmid: 17291758
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):10908-13
references.pmid: 20534491
references.citation: Cell Mol Life Sci. 2010 Aug;67(15):2563-89
references.pmid: 20333435