title: Intestinal expression of metal transporters in Wilson's disease.
abstract: In Wilson's disease (WND), biallelic ATP7B gene mutation is responsible for pathological copper accumulation in the liver, brain and other organs. It has been proposed that copper transporter 1 (CTR1) and the divalent metal transporter 1 (DMT1) translocate copper across the human intestinal epithelium, while Cu-ATPases: ATP7A and ATP7B serve as copper efflux pumps. In this study, we investigated the expression of CTR1, DMT1 and ATP7A in the intestines of both WND patients and healthy controls to examine whether any adaptive mechanisms to systemic copper overload function in the enterocytes. Duodenal biopsy samples were taken from 108 patients with Wilson's disease and from 90 controls. CTR1, DMT1, ATP7A and ATP7B expression was assessed by polymerase chain reaction and Western blot. Duodenal CTR1 mRNA and protein expression was decreased in WND patients in comparison to control subjects, while ATP7A mRNA and protein production was increased. The variable expression of copper transporters may serve as a defense mechanism against systemic copper overload resulting from functional impairment of ATP7B.
authors: Department of Clinical and Experimental Pharmacology, Medical University of Warsaw, ul. Krakowskie Przedmieście 26/28, 00-927, Warsaw, Poland, aprzybylkowski@wum.edu.pl.
authors: Adam
authors: A
authors: Przybyłkowski
authors: Grażyna
authors: G
authors: Gromadzka
authors: Adriana
authors: A
authors: Wawer
authors: Tomasz
authors: T
authors: Grygorowicz
authors: Anna
authors: A
authors: Cybulska
authors: Anna
authors: A
authors: Członkowska
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D003300:Copper / Q000097:blood*; D000079923:Copper Transporter 1; D000073840:Copper-Transporting ATPases; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006527:Hepatolenticular Degeneration / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017136:Ion Transport; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; C110547:DMRT1 protein; D012333:RNA, Messenger; C490079:SLC31A1 protein, human; D014157:Transcription Factors; D003300:Copper; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases
references: Clin Biochem Rev. 2005 Aug;26(3):47-9
references: 16450011
references: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5302-7
references: 16567646
references: Clin Cancer Res. 2004 Oct 1;10(19):6744-9
references: 15475465
references: PLoS One. 2012;7(6):e38327
references: 22802922
references: Am J Gastroenterol. 1999 Feb;94(2):334-8
references: 10022625
references: Adv Pediatr. 1994;41:263-304
references: 7992686
references: Am J Physiol Gastrointest Liver Physiol. 2005 May;288(5):G1007-14
references: 15591161
references: Clin Cancer Res. 2004 Jul 15;10(14):4661-9
references: 15269138
references: Clin Cancer Res. 2004 Jul 1;10(13):4578-88
references: 15240550
references: Liver Int. 2003 Jun;23(3):139-42
references: 12955875
references: J Clin Invest. 1954 Nov;33(11):1487-501
references: 13211803
references: J Biol Chem. 2007 Sep 7;282(36):26471-80
references: 17627945
references: Pediatrics. 1962 May;29:764-79
references: 14472668
references: J Lab Clin Med. 1961 Jul;58:161-8
references: 13739892
references: Mol Pharmacol. 2012 Mar;81(3):455-64
references: 22172574
references: J Biol Chem. 2005 Oct 28;280(43):36221-7
references: 16081413
references: Anal Biochem. 1976 May 7;72:248-54
references: 942051
references: Hepatology. 2009 Dec;50(6):1783-95
references: 19937698
references: J Biol Chem. 2002 Oct 25;277(43):40253-9
references: 12177073
references: Mol Cancer Ther. 2012 Jun;11(6):1221-5
references: 22491798
references: Pflugers Arch. 2004 Feb;447(5):571-9
references: 14530973
references: Gastroenterology. 2003 Feb;124(2):335-45
references: 12557139
references: J Nutr. 2006 Jan;136(1):21-6
references: 16365053
references: Cell Metab. 2010 May 5;11(5):353-63
references: 20444417
references: J Anat. 2008 Sep;213(3):232-40
references: 18673401
references: Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10854-9
references: 9724794
references: Biol Res. 2006;39(1):79-85
references: 16629167
references: Future Med Chem. 2009 Sep;1(6):1125-42
references: 20454597
references: Proc Natl Acad Sci U S A. 1985 Mar;82(6):1819-21
references: 3856863
references: Am J Physiol Cell Physiol. 2011 Mar;300(3):C588-99
references: 21191107
references: J Biol Chem. 2011 May 6;286(18):16355-62
references: 21398519
references: Am J Physiol Cell Physiol. 2003 Jun;284(6):C1525-30
references: 12734107
references: Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1181-94
references: 17158254
references: Exp Clin Endocrinol Diabetes. 1998;106(6):506-13
references: 10079033
references: J Biol Chem. 2010 Oct 15;285(42):32385-92
references: 20699218
references: Arch Biochem Biophys. 2007 Jul 15;463(2):149-67
references: 17531189
references: J Biol Chem. 2003 Apr 11;278(15):13302-8
references: 12551905
references: Mol Pharmacol. 2008 Sep;74(3):705-13
references: 18483225