title: ClC-3 chloride channel is upregulated by hypertrophy and inflammation in rat and canine pulmonary artery.
abstract: Cl- channels have been implicated in essential cellular functions including volume regulation, progression of cell cycle, cell proliferation and contraction, but the physiological functions of the ClC-3 channel are controversial. We tested the hypothesis that the ClC-3 gene (ClCn-3) is upregulated in hypertensive pulmonary arteries of monocrotaline-treated rats, and upregulated ClC-3 channel aids viability of pulmonary artery smooth muscle cells (PASMCs). Experimental pulmonary hypertension was induced in rats by a single subcutaneous administration of monocrotaline (60 mg kg(-1)). Injected animals developed characteristic features of pulmonary hypertension including medial hypertrophy of pulmonary arteries and right ventricular hypertrophy. Reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry and Western immunoblot analysis indicated that histopathological alterations were associated with upregulation of the ClC-3 mRNA and protein expression in both smooth muscle cells of hypertensive pulmonary arteries and in cardiac myocytes. RT-PCR analysis of mRNA, extracted from canine cultured PASMCs, indicated that incubation with the inflammatory mediators endothelin-1 (ET-1), platelet-derived growth factor (PDGF), interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF alpha), but not transforming growth factor beta (TGFbeta), upregulated ClC-3 mRNA. Adenovirus-mediated delivery and overexpression of ClC-3 in canine PASMCs improved cell viability against increasing concentrations of hydrogen peroxide (H2O2, range 50-250 microM). In conclusion, upregulation of ClC-3 in rat hypertensive lung and heart is a novel observation. Our functional data suggest that upregulation of ClC-3 is an adaptive response of inflamed pulmonary artery, which enhances the viability of PASMCs against reactive oxygen species.
authors.affiliation: Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557-0270, USA.
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Dai
authors.forename: Shaner
authors.initials: S
authors.lastname: Bongalon
authors.forename: William J
authors.initials: WJ
authors.lastname: Hatton
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Hume
authors.forename: Ilia A
authors.initials: IA
authors.lastname: Yamboliev
mesh_terms: D000818:Animals; D001167:Arteritis / Q000378:metabolism; D018118:Chloride Channels / Q000378:metabolism*; D004285:Dogs; D005260:Female; D006973:Hypertension / Q000378:metabolism; D006984:Hypertrophy / Q000378:metabolism; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D011651:Pulmonary Artery / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: D018118:Chloride Channels; C115376:ClC-3 channel
references.citation: Br J Pharmacol. 1999 Nov;128(5):1098-104
references.pmid: 10556948
references.citation: Atherosclerosis. 2003 Feb;166(2):291-301
references.pmid: 12535742
references.citation: J Heart Lung Transplant. 1999 Nov;18(11):1041-53
references.pmid: 10598727
references.citation: IUBMB Life. 1999 Jul;48(1):41-7
references.pmid: 10791914
references.citation: Swiss Med Wkly. 2003 Feb 22;133(7-8):103-10
references.pmid: 12644956
references.citation: Toxicol Appl Pharmacol. 2003 Mar 15;187(3):178-85
references.pmid: 12662901
references.citation: Lancet. 2003 May 3;361(9368):1533-44
references.pmid: 12737878
references.citation: Am J Physiol Heart Circ Physiol. 2003 Oct;285(4):H1453-63
references.pmid: 12816749
references.citation: J Gen Physiol. 2003 Dec;122(6):689-702
references.pmid: 14610020
references.citation: Clin Sci (Lond). 2004 Mar;106(3):219-34
references.pmid: 14733610
references.citation: J Biol Chem. 2004 Apr 2;279(14):13301-4
references.pmid: 14761962
references.citation: J Physiol. 2004 Apr 15;556(Pt 2):353-68
references.pmid: 14754994
references.citation: Sheng Li Xue Bao. 2004 Apr 25;56(2):230-6
references.pmid: 15127135
references.citation: Curr Pharm Des. 2004;10(14):1611-26
references.pmid: 15134560
references.citation: J Physiol. 2004 Jun 1;557(Pt 2):343
references.pmid: 15020689
references.citation: Am J Physiol Heart Circ Physiol. 2004 Aug;287(2):H533-44
references.pmid: 15277197
references.citation: J Immunol Methods. 1983 Dec 16;65(1-2):55-63
references.pmid: 6606682
references.citation: J Clin Invest. 1988 Dec;82(6):2045-55
references.pmid: 3198764
references.citation: Am J Physiol. 1988 Dec;255(6 Pt 2):H1484-91
references.pmid: 3144186
references.citation: J Clin Invest. 1995 Jun;95(6):2474-82
references.pmid: 7769093
references.citation: Mol Biotechnol. 1995 Jun;3(3):207-20
references.pmid: 7552690
references.citation: Ann N Y Acad Sci. 1995 Sep 7;766:416-30
references.pmid: 7486687
references.citation: Arterioscler Thromb Vasc Biol. 1995 Dec;15(12):2200-6
references.pmid: 7489243
references.citation: Br J Pharmacol. 1995 Oct;116(4):2267-73
references.pmid: 8564258
references.citation: J Biol Chem. 1996 Jan 5;271(1):77-82
references.pmid: 8550628
references.citation: Circ Res. 1996 Dec;79(6):1131-42
references.pmid: 8943951
references.citation: Gen Pharmacol. 1996 Oct;27(7):1079-89
references.pmid: 8981052
references.citation: Am J Physiol. 1997 Feb;272(2 Pt 1):C667-74
references.pmid: 9124311
references.citation: Am J Pathol. 1997 Apr;150(4):1349-60
references.pmid: 9094991
references.citation: J Physiol. 2000 Dec 1;529 Pt 2:385-94
references.pmid: 11101648
references.citation: Atherosclerosis. 2001 Feb 1;154(2):377-85
references.pmid: 11166770
references.citation: J Physiol. 2001 May 1;532(Pt 3):581
references.pmid: 11313429
references.citation: J Biol Chem. 2001 Jun 8;276(23):20093-100
references.pmid: 11274166
references.citation: Exp Gerontol. 2001 Jul;36(7):969-87
references.pmid: 11404045
references.citation: Jpn J Pharmacol. 2001 Jul;86(3):310-5
references.pmid: 11488431
references.citation: Curr Biol. 2001 Aug 7;11(15):R620-8
references.pmid: 11516971
references.citation: Nature. 1997 Nov 27;390(6658):417-21
references.pmid: 9389484
references.citation: Pharmacol Res. 1997 Nov;36(5):339-51
references.pmid: 9441724
references.citation: Prog Biophys Mol Biol. 1997;68(1):69-119
references.pmid: 9481145
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2509-14
references.pmid: 9482916
references.citation: J Physiol. 1998 Mar 15;507 ( Pt 3):729-36
references.pmid: 9508834
references.citation: Free Radic Biol Med. 1998 Oct;25(6):694-702
references.pmid: 9801070
references.citation: Biochem J. 1999 Jan 15;337 ( Pt 2):171-7
references.pmid: 9882612
references.citation: J Mol Cell Cardiol. 1999 Mar;31(3):657-66
references.pmid: 10198195
references.citation: Biochem J. 1999 May 1;339 ( Pt 3):481-8
references.pmid: 10215583
references.citation: J Vasc Res. 2004 Sep-Oct;41(5):412-21
references.pmid: 15467300
references.citation: Clin Chest Med. 2001 Sep;22(3):433-49, viii
references.pmid: 11590839
references.citation: Physiol Rev. 2002 Apr;82(2):503-68
references.pmid: 11917096
references.citation: J Physiol. 2002 May 1;540(Pt 3):883-93
references.pmid: 11986377
references.citation: J Cell Biol. 2002 Aug 5;158(3):435-44
references.pmid: 12163466
references.citation: Antioxid Redox Signal. 2002 Aug;4(4):563-8
references.pmid: 12230867
references.citation: Biochem Biophys Res Commun. 2002 Nov 1;298(3):408-13
references.pmid: 12413956
references.citation: Circ Res. 2002 Nov 15;91(10):E28-32
references.pmid: 12433844
references.citation: Prog Cardiovasc Dis. 2002 Nov-Dec;45(3):173-202
references.pmid: 12525995