Down-regulation of ASICs Current and the Calcium Transients by Disrupting PICK1 Protects Primary Cultured Mouse Cortical Neurons from OGD-Rep Insults

Overview

Journal Int J Clin Exp Pathol

Specialty Pathology

Date 2015 Dec 1

PMID 26617735

Citations 1

Authors

Jin Cheng

Yu Chen

Hui Xing

Hua Jiang

Xihong Ye

Affiliations

Soon will be listed here.

Abstract

Acid sensing ion channels (ASICs), activated by lowering extracellular pH, play an important role in normal synaptic transmission in brain and in the pathology of brain ischemia. ASICs activation involving in glutamate receptor-independent ischemic brain injury has been generally accepted, and PICK1 is recently shown to be one of partner proteins interacting with ASICs through its PDZ domain. Here we showed that ASICs and PICK1 played key roles in OGD-Rep process. In wild-type cultured cortical neurons, not only the amplitude of ASICs current and the calcium transients induced by acidosis were both increased after OGD-Rep, but also the total protein levels of ASIC1 and ASIC2a were up-regulated progressively after ischemia insults, indicating that ASICs play a vital role in neuronal ischemia. However, these activities were reversed with PICK1-knockout after OGD-Rep, accompanied with the dramatically down-regulating the protein abundances of ASIC1 and ASIC2a, which suggested the neuroprotection activity in brain ischemia by PICK1-knockout. These results indicate that knocking-out PICK1 gene casts the neuroprotection effect by reducing ASICs current and the calcium transients in OGD-Rep neuronal cells, which will offer a promising strategy in the therapy of brain ischemia.

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References

Jin W, Shen C, Jing L, Zha X, Xia J . PICK1 regulates the trafficking of ASIC1a and acidotoxicity in a BAR domain lipid binding-dependent manner. Mol Brain. 2010; 3:39. PMC: 3018362. DOI: 10.1186/1756-6606-3-39. View

Hu Z, Huang C, Fu H, Jin Y, Wu W, Xiong Q . Disruption of PICK1 attenuates the function of ASICs and PKC regulation of ASICs. Am J Physiol Cell Physiol. 2010; 299(6):C1355-62. DOI: 10.1152/ajpcell.00569.2009. View

Lai T, Shyu W, Wang Y . Stroke intervention pathways: NMDA receptors and beyond. Trends Mol Med. 2011; 17(5):266-75. DOI: 10.1016/j.molmed.2010.12.008. View

Sherwood T, Lee K, Gormley M, Askwith C . Heteromeric acid-sensing ion channels (ASICs) composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death. J Neurosci. 2011; 31(26):9723-34. PMC: 3160670. DOI: 10.1523/JNEUROSCI.1665-11.2011. View

Zeng W, Liu D, Duan B, Song X, Wang X, Wei D . Molecular mechanism of constitutive endocytosis of Acid-sensing ion channel 1a and its protective function in acidosis-induced neuronal death. J Neurosci. 2013; 33(16):7066-78. PMC: 4201763. DOI: 10.1523/JNEUROSCI.5206-12.2013. View

Chu X, Grasing K, Wang J . Acid-sensing ion channels contribute to neurotoxicity. Transl Stroke Res. 2013; 5(1):69-78. PMC: 5776693. DOI: 10.1007/s12975-013-0305-y. View

Uria-Avellanal C, Robertson N . Na⁺/H⁺ exchangers and intracellular pH in perinatal brain injury. Transl Stroke Res. 2014; 5(1):79-98. PMC: 3913853. DOI: 10.1007/s12975-013-0322-x. View

Perez J, Khatri L, Chang C, Srivastava S, Osten P, Ziff E . PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. J Neurosci. 2001; 21(15):5417-28. PMC: 6762658. View

Johnson M, Jin K, Minami M, Chen D, Simon R . Global ischemia induces expression of acid-sensing ion channel 2a in rat brain. J Cereb Blood Flow Metab. 2001; 21(6):734-40. DOI: 10.1097/00004647-200106000-00011. View

10.

Reeh P, Kress M . Molecular physiology of proton transduction in nociceptors. Curr Opin Pharmacol. 2001; 1(1):45-51. DOI: 10.1016/s1471-4892(01)00014-5. View

11.

Hruska-Hageman A, Wemmie J, Price M, Welsh M . Interaction of the synaptic protein PICK1 (protein interacting with C kinase 1) with the non-voltage gated sodium channels BNC1 (brain Na+ channel 1) and ASIC (acid-sensing ion channel). Biochem J. 2002; 361(Pt 3):443-50. PMC: 1222326. DOI: 10.1042/0264-6021:3610443. View

12.

Chen J, Daggett H, De Waard M, Heinemann S, Hoshi T . Nitric oxide augments voltage-gated P/Q-type Ca(2+) channels constituting a putative positive feedback loop. Free Radic Biol Med. 2002; 32(7):638-49. DOI: 10.1016/s0891-5849(02)00748-7. View

13.

Baron A, Deval E, Salinas M, Lingueglia E, Voilley N, Lazdunski M . Protein kinase C stimulates the acid-sensing ion channel ASIC2a via the PDZ domain-containing protein PICK1. J Biol Chem. 2002; 277(52):50463-8. DOI: 10.1074/jbc.M208848200. View

14.

Alvarez de la Rosa D, Krueger S, Kolar A, Shao D, Fitzsimonds R, Canessa C . Distribution, subcellular localization and ontogeny of ASIC1 in the mammalian central nervous system. J Physiol. 2003; 546(Pt 1):77-87. PMC: 2342460. DOI: 10.1113/jphysiol.2002.030692. View

15.

Deval E, Salinas M, Baron A, Lingueglia E, Lazdunski M . ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1. J Biol Chem. 2004; 279(19):19531-9. DOI: 10.1074/jbc.M313078200. View

16.

Yermolaieva O, Leonard A, Schnizler M, Abboud F, Welsh M . Extracellular acidosis increases neuronal cell calcium by activating acid-sensing ion channel 1a. Proc Natl Acad Sci U S A. 2004; 101(17):6752-7. PMC: 404117. DOI: 10.1073/pnas.0308636100. View

17.

Seta K, Yuan Y, Spicer Z, Lu G, Bedard J, Ferguson T . The role of calcium in hypoxia-induced signal transduction and gene expression. Cell Calcium. 2004; 36(3-4):331-40. DOI: 10.1016/j.ceca.2004.02.006. View

18.

Cadiou H, Studer M, Jones N, Smith E, Ballard A, McMahon S . Modulation of acid-sensing ion channel activity by nitric oxide. J Neurosci. 2007; 27(48):13251-60. PMC: 6673420. DOI: 10.1523/JNEUROSCI.2135-07.2007. View

19.

Kim K, Jin Y . Neuronal responses to stress and injury in C. elegans. FEBS Lett. 2015; 589(14):1644-52. PMC: 4458507. DOI: 10.1016/j.febslet.2015.05.005. View

20.

Xiong Z, Zhu X, Chu X, Minami M, Hey J, Wei W . Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell. 2004; 118(6):687-98. DOI: 10.1016/j.cell.2004.08.026. View