title: Involvement of acid-sensing ion channel 1a in functions of cultured human retinal pigment epithelial cells.
abstract: In the retina, pH fluctuations may play an important role in adapting retinal responses to different light intensities and are involved in the fine tuning of visual perception. Acidosis occurs in the subretinal space (SRS) under pathological conditions such as age-related macular degeneration (AMD). Although it is well known that many transporters in the retinal pigment epithelium (RPE) cells can maintain pH homeostasis efficiently, other receptors in RPE may also be involved in sensing acidosis, such as acid-sensing ion channels (ASICs). In this study, we investigated whether ASIC1a was expressed in the RPE cells and whether it was involved in the function of these cells. Real-time RT-PCR and Western blotting were used to analyze the ASIC1a expression in ARPE-19 cells during oxidative stress induced by hydrogen peroxide (H(2)O(2)). Furthermore, inhibition or over-expression of ASIC1a in RPE cells was obtained using inhibitors (amiloride and PCTx1) or by the transfection of cDNA encoding hASIC1a. Cell viability was determined by using the MTT assay. The real-time RT-PCR and Western blotting results showed that both the mRNA and protein of ASIC1a were expressed in RPE cells. Inhibition of ASICs by amiloride in normal RPE cells resulted in cell death, indicating that ASICs play an important physiological role in RPE cells. Furthermore, over-expression of ASIC1a in RPE cells prolonged cell survival under oxidative stress induced by H(2)O(2). In conclusion, ASIC1a is functionally expressed in RPE cells and may play an important role in the physiological function of RPE cells by protecting them from oxidative stress.
authors: Department of Plastic Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
authors: Jian
authors: J
authors: Tan
authors: Department of Plastic Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
authors: Yi-Pin
authors: YP
authors: Xu
authors: Department of Plastic Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
authors: Guang-Peng
authors: GP
authors: Liu
authors: Department of Plastic Surgery, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China. dryxh@189.cn.
authors: Xin-Hai
authors: XH
authors: Ye
mesh_terms: D062565:Acid Sensing Ion Channels / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000378:metabolism*
chemical_list: C568266:ASIC1 protein, human; D062565:Acid Sensing Ion Channels
references: Nature. 2007 Sep 20;449(7160):316-23
references: 17882215
references: Nature. 1998 Jul 9;394(6689):192-5
references: 9671304
references: Mol Vis. 2002 Jul 09;8:221-5
references: 12107409
references: Biochim Biophys Acta. 2005 Aug 15;1745(1):1-6
references: 16085050
references: J Neurosci. 2006 May 17;26(20):5329-39
references: 16707785
references: Invest Ophthalmol Vis Sci. 1989 Aug;30(8):1691-9
references: 2759786
references: Curr Opin Neurobiol. 1998 Jun;8(3):418-24
references: 9687356
references: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3573-8
references: 19218436
references: Curr Opin Drug Discov Devel. 2009 Sep;12(5):693-704
references: 19736627
references: Neuroreport. 2000 Jul 14;11(10):2217-22
references: 10923674
references: J Cell Sci Suppl. 1993;17:189-95
references: 8144697
references: Prog Retin Eye Res. 2005 Mar;24(2):275-306
references: 15610977
references: Mol Vis. 2008;14:2340-8
references: 19096717
references: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6752-7
references: 15082829
references: Exp Eye Res. 2003 Apr;76(4):493-504
references: 12634113
references: J Biol Chem. 1994 Jul 8;269(27):17954-9
references: 8027053
references: Exp Eye Res. 1999 Jul;69(1):21-32
references: 10375446
references: J Neurochem. 2004 Feb;88(4):885-90
references: 14756809
references: Nature. 1997 Mar 13;386(6621):173-7
references: 9062189
references: J Neurosci. 2006 May 24;26(21):5800-9
references: 16723538
references: Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5767-72
references: 18055830
references: Ophthalmology. 1984 Jun;91(6):613-25
references: 6205340
references: J Neurosci. 2004 Feb 4;24(5):1005-12
references: 14762118
references: J Physiol. 1999 Sep 1;519 Pt 2:323-33
references: 10457052
references: J Neurochem. 2005 Jul;94(1):120-8
references: 15953355
references: Prog Retin Eye Res. 2000 Mar;19(2):205-21
references: 10674708
references: Physiol Rev. 2005 Jul;85(3):845-81
references: 15987797
references: J Biol Chem. 1997 Aug 22;272(34):20975-8
references: 9261094
references: Ophthalmic Res. 1992;24(4):243-52
references: 1436983
references: J Biol Chem. 1997 Nov 21;272(47):29778-83
references: 9368048