ClC-3 Chloride Channel is Upregulated by Hypertrophy and Inflammation in Rat and Canine Pulmonary Artery

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 2005 Feb 22

PMID 15723096

Citations 26

Authors

Yan-Ping Dai

Shaner Bongalon

William J Hatton

Joseph R Hume

Ilia A Yamboliev

Affiliations

Soon will be listed here.

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.

Citing Articles

Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.

Wan Y, Guo S, Zhen W, Xu L, Chen X, Liu F Nat Commun. 2024; 15(1):6654.

PMID: 39107281 PMC: 11303396. DOI: 10.1038/s41467-024-50975-w.

ANO1, CaV1.2, and IP3R form a localized unit of EC-coupling in mouse pulmonary arterial smooth muscle.

Akin E, Aoun J, Jimenez C, Mayne K, Baeck J, Young M J Gen Physiol. 2023; 155(11).

PMID: 37702787 PMC: 10499037. DOI: 10.1085/jgp.202213217.

Chloride Channel-3 (ClC-3) Modifies the Trafficking of Leucine-Rich Repeat-Containing 8A (LRRC8A) Anion Channels.

Stark R, Nguyen H, Bacon M, Rohrbough J, Choi H, Lamb F J Membr Biol. 2022; 256(2):125-135.

PMID: 36322172 PMC: 10085862. DOI: 10.1007/s00232-022-00271-9.

MiR-1-3p that correlates with left ventricular function of HCM can serve as a potential target and differentiate HCM from DCM.

Li M, Chen X, Chen L, Chen K, Zhou J, Song J J Transl Med. 2018; 16(1):161.

PMID: 29885652 PMC: 5994246. DOI: 10.1186/s12967-018-1534-3.

Betaine Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats via Inhibiting Inflammatory Response.

Yang J, Zhou R, Zhang M, Tan H, Yu J Molecules. 2018; 23(6).

PMID: 29861433 PMC: 6100216. DOI: 10.3390/molecules23061274.

References

Nakazawa H, Hori M, Ozaki H, Karaki H . Mechanisms underlying the impairment of endothelium-dependent relaxation in the pulmonary artery of monocrotaline-induced pulmonary hypertensive rats. Br J Pharmacol. 1999; 128(5):1098-104. PMC: 1571722. DOI: 10.1038/sj.bjp.0702878. View

Cao Z, Hardej D, Trombetta L, Trush M, Li Y . Induction of cellular glutathione and glutathione S-transferase by 3H-1,2-dithiole-3-thione in rat aortic smooth muscle A10 cells: protection against acrolein-induced toxicity. Atherosclerosis. 2003; 166(2):291-301. DOI: 10.1016/s0021-9150(02)00331-3. View

Rabinovitch M . Pulmonary hypertension: pathophysiology as a basis for clinical decision making. J Heart Lung Transplant. 1999; 18(11):1041-53. DOI: 10.1016/s1053-2498(99)00015-7. View

Davies K . The broad spectrum of responses to oxidants in proliferating cells: a new paradigm for oxidative stress. IUBMB Life. 2000; 48(1):41-7. DOI: 10.1080/713803463. View

Nicod L . Pulmonary hypertension. Swiss Med Wkly. 2003; 133(7-8):103-10. DOI: 10.4414/smw.2003.10026. View

Chen M, Lai Y . Tachykinin dysfunction attenuates monocrotaline-induced pulmonary hypertension. Toxicol Appl Pharmacol. 2003; 187(3):178-85. DOI: 10.1016/s0041-008x(02)00070-4. View

Runo J, Loyd J . Primary pulmonary hypertension. Lancet. 2003; 361(9368):1533-44. DOI: 10.1016/S0140-6736(03)13167-4. View

Wang G, Hatton W, Wang G, Zhong J, Yamboliev I, Duan D . Functional effects of novel anti-ClC-3 antibodies on native volume-sensitive osmolyte and anion channels in cardiac and smooth muscle cells. Am J Physiol Heart Circ Physiol. 2003; 285(4):H1453-63. DOI: 10.1152/ajpheart.00244.2003. View

Browe D, Baumgarten C . Stretch of beta 1 integrin activates an outwardly rectifying chloride current via FAK and Src in rabbit ventricular myocytes. J Gen Physiol. 2003; 122(6):689-702. PMC: 2229598. DOI: 10.1085/jgp.200308899. View

10.

Hamilton C, Miller W, Al-Benna S, Brosnan M, Drummond R, McBride M . Strategies to reduce oxidative stress in cardiovascular disease. Clin Sci (Lond). 2004; 106(3):219-34. DOI: 10.1042/CS20030379. View

11.

Varela D, Simon F, Riveros A, Jorgensen F, Stutzin A . NAD(P)H oxidase-derived H(2)O(2) signals chloride channel activation in cell volume regulation and cell proliferation. J Biol Chem. 2004; 279(14):13301-4. DOI: 10.1074/jbc.C400020200. View

12.

Robinson N, Huang P, Kaetzel M, Lamb F, Nelson D . Identification of an N-terminal amino acid of the CLC-3 chloride channel critical in phosphorylation-dependent activation of a CaMKII-activated chloride current. J Physiol. 2004; 556(Pt 2):353-68. PMC: 1664934. DOI: 10.1113/jphysiol.2003.058032. View

13.

Wang L, Chen L, Jacob T . ClC-3 expression in the cell cycle of nasopharyngeal carcinoma cells. Sheng Li Xue Bao. 2004; 56(2):230-6. View

14.

Bergamini C, Gambetti S, Dondi A, Cervellati C . Oxygen, reactive oxygen species and tissue damage. Curr Pharm Des. 2004; 10(14):1611-26. DOI: 10.2174/1381612043384664. View

15.

Greenwood I . CLC-3 knockout hints at swelling-activated chloride channel complexity. J Physiol. 2004; 557(Pt 2):343. PMC: 1665095. DOI: 10.1113/jphysiol.2004.063750. View

16.

Wang G, McCrudden C, Dai Y, Horowitz B, Hume J, Yamboliev I . Hypotonic activation of volume-sensitive outwardly rectifying chloride channels in cultured PASMCs is modulated by SGK. Am J Physiol Heart Circ Physiol. 2004; 287(2):H533-44. DOI: 10.1152/ajpheart.00228.2003. View

17.

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

18.

Lewis M, Whatley R, Cain P, McIntyre T, Prescott S, Zimmerman G . Hydrogen peroxide stimulates the synthesis of platelet-activating factor by endothelium and induces endothelial cell-dependent neutrophil adhesion. J Clin Invest. 1988; 82(6):2045-55. PMC: 442787. DOI: 10.1172/JCI113825. View

19.

Rosenberg H, Rabinovitch M . Endothelial injury and vascular reactivity in monocrotaline pulmonary hypertension. Am J Physiol. 1988; 255(6 Pt 2):H1484-91. DOI: 10.1152/ajpheart.1988.255.6.H1484. View

20.

Fujitani Y, Ninomiya H, Okada T, Urade Y, Masaki T . Suppression of endothelin-1-induced mitogenic responses of human aortic smooth muscle cells by interleukin-1 beta. J Clin Invest. 1995; 95(6):2474-82. PMC: 295928. DOI: 10.1172/JCI117948. View