酸敏感离子通道1a在自身免疫性疾病发病机制中的研究进展
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摘要
酸敏感离子通道(acid-sensing ion channels,ASICs)是在外周和中枢神经系统中广泛表达的质子门控的阳离子通道,ASIC1a作为其重要的组成部分在许多生理和病理过程中起重要作用。作为细胞外质子的关键受体,ASIC1a参与涉及组织酸中毒的多种病理生理过程,如疼痛、炎症、癫痫发作、多发性硬化等。自身免疫疾病是机体在应对自身抗原发生免疫反应时,过度活化的T、B细胞导致机体多组织器官受损的慢性炎症性疾病。近年来研究发现,ASIC1a在多种自身免疫性疾病发生中发挥着重要作用,该文就ASIC1a的生物学特征作简要综述,重点探讨ASIC1a在自身免疫性疾病发病机制中的研究进展。
Acid-sensing ion channels( ASICs) are proton-gated channels expressed widely in the central nervous systems and peripheral tissues,among which ASIC1 a is a core part and plays an important role in many physiological and pathological processes. As a key receptor for extracellular protons,ASIC1 a is involved in a variety of pathophysiological processes involving tissue acidosis,such as pain,inflammation,seizures and multiple sclerosis. Autoimmune disease is a chronic inflammatory disease,and the excessive activation of T,B cells leads to multiple tissue and organ damage when the body responds to autoantigen immune response. In recent years, studies have found that ASIC1 a plays an important role in the development of various autoimmune diseases. In this paper,the biological characteristics of ASIC1 a are briefly reviewed,and the research progress of ASIC1 a in the development and progression of autoimmune diseases is discussed.
Acid-sensing ion channels( ASICs) are proton-gated channels expressed widely in the central nervous systems and peripheral tissues,among which ASIC1 a is a core part and plays an important role in many physiological and pathological processes. As a key receptor for extracellular protons,ASIC1 a is involved in a variety of pathophysiological processes involving tissue acidosis,such as pain,inflammation,seizures and multiple sclerosis. Autoimmune disease is a chronic inflammatory disease,and the excessive activation of T,B cells leads to multiple tissue and organ damage when the body responds to autoantigen immune response. In recent years, studies have found that ASIC1 a plays an important role in the development of various autoimmune diseases. In this paper,the biological characteristics of ASIC1 a are briefly reviewed,and the research progress of ASIC1 a in the development and progression of autoimmune diseases is discussed.
引文
[1]周仁鹏,陈飞虎.酸敏感离子通道在类风湿关节炎中作用的研究进展[J].中国药理学通报,2015,31(3):315-8.[1]Zhou R P,Chen F H.Acid-sensing ion channels in the role of rheumatoid arthritis research progress[J].Chin Pharmacol Bull,2015,31(3):315-8.
[2]Lin Y C,Liu Y C,Huang Y Y,et al.High-density expression of Ca2+-permeable ASIC1a channels in NG2 glia of rat hippocampus[J].PLo S One,2010,5(9):e12665.
[3]Baconguis I,Bohlen C J,Goehring A,et al.X-ray structure of acid-sensing ion channel 1-snake toxin complex revealsopen state of a Na+-selective channel[J].Cell,2014,156(4):717-29.
[4]Deval E.Acid-sensing ion channels and nociception in the peripheral and central nervous systems[J].Neuropharmacology,2015,94(7):49-57.
[5]Jahr H,van Driel M,van Osch G J,et al.Identification of acidsensing ion channels in bone[J].Biochem Biophys Res Commun,2005,337(1):349-54.
[6]袁凤来,陈飞虎,黄学应,等.酸敏感离子通道在大鼠佐剂性关节炎关节软骨中的表达[J].中华风湿病学杂志,2008,12(5):321-4.[6]Yuan F L,Chen F H,Huang X Y,et al.Expression of acid-sensing ion channels in articular cartilage of rat adjuvant arthritis.[J].Chin J Rheumatol,2008,12(5):321-4.
[7]Chu X P,Grasing K A.Acid-sensing ion channels contribute to neurotoxicity[J].Transl Stroke Res,2014,5(1):69-78.
[8]Leng T D,Xiong Z G.The pharmacology and therapeutic potential of small molecule inhibitors of acid-sensing ion channels in stroke intervention[J].Acta Pharmacol Sin,2013,34(1):33-8.
[9]Martinez D,Vermeulen M,Trevani A,et al.Extracellular acidosis induces neutrophil activation by a mechanism dependent on activation of phosphatidylinositol 3-kinase/Akt and ERK pathways[J].J Immunol,2006,176(2):1163-71.
[10]Rong C,Chen F H,Jiang S,et al.Inhibition of acid-sensing ion channels by amiloride protects rat articular chondrocytes from acidinduced apoptosis via a mitochondrial-mediated pathway[J].Cell Biol Int,2012,36(7):635-41.
[11]Yuan F L,Chen F H,Lu W G,et al.Acid-sensing ion channel1a mediates acid-induced increases in intracellular calcium in rat articular chondrocytes[J].Mol Cell Biochem,2011,340(1-2):153-9.
[12]江晟,陈飞虎,陈寸知,等.siRNA沉默ASIC1a基因对佐剂性关节炎大鼠关节软骨细胞凋亡的影响研究[J].中国临床药理学与治疗学,2012,17(3):256-62.[12]Jiang S,Chen F H,Chen C Z,et al.Effect of siRNA silencing ASIC1a gene on apoptosis of articular chondrocytes in rats with adjuvant arthritis[J].Chin J Clin Pharmacol Ther,2012,17(3):256-62.
[13]Auberger P.Autophagy.A key mechanism of oncogenesis and resistance in leukemia[J].Blood,2017,129(5):547-52.
[14]张晨晨,唐杰,胡伟,等.酸敏感离子通道1a在酸诱导的大鼠关节软骨细胞自噬的作用及其机制研[J].中国药理学通报,2013,29(8):1092-8.[14]Zhang C C,Tang J,Hu W,et al.Effects of acid-sensing ion channel 1a on acid-induced autophagy of rat articular chondrocytes and its mechanism[J].Chin Pharmacol Bull,2013,29(8):1092-8.
[15]高文凡,陈飞虎,葛金芳,等.钙络合剂BAPTA-AM对胞外酸化诱导大鼠关节软骨细胞自噬作用的影响及其可能机制[J].中国药理学通报,2015,31(5):655-9.[15]Gao W F,Chen F H,Ge J F,et al.Effects of BAPTA-AM on autophagy of rat articular chondrocytes induced by extracellular acidification and its possible mechanism[J].Chin Pharmacol Bull,2015,31(5):655-9.
[16]Boiko N,Kucher V,Eaton B A.Inhibition of neuronal degenerin/epithelial Na+channels by the multiple sclerosis drug 4-aminopyridine[J].J Biol Chem,2013,288(13):9418-27.
[17]Vergo S,Craner M J,Etzensperger R,et al.Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model[J].Brain,2011,134(Pt2):571-84.
[18]Friese M A,Craner M J,Etzensperger R,et al.Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system[J].Nat Med,2007,13(12):1483-9.
[19]Arun T,Tomassini V,Sbardella E,et al.Targeting ASIC1 in primary progressive multiple sclerosis:evidence of neuroprotection with amiloride[J].Brain,2013,136(Pt 1):106-15.
[20]St rling J.Type 1 diabetes candidate genes linked to pancreatic islet cell inflammation and beta-cell apoptosis[J].Genes,2017,8(2):pii:E72.
[21]Chai S,Li M,Branigan D,et al.Activation of acid-sensing ion channel 1a(ASIC1a)by surface trafficking[J].J Biol Chem,2010,285(17):13002-11.
[22]Duan B,Liu D S,Huang Y,et al.PI3-kinase/Akt pathway-regulated membrane insertion of acid-sensing ion channel 1a underlies BDNF-induced pain hypersensitivity[J].J Neurosci,2012,32(18):6351-63.
[23]Radu B M,Dumitrescu D I,Marin A,et al.Advanced type 1 diabetes is associated with ASIC alterations in mouse lower thoracic dorsal root ganglia neurons[J].Cell Biochem Biophys,2014,68(1):9-23
[24]吴新安,胡波,陈慧慧,等.阿米洛利对硝普钠诱导的骨性关节炎大鼠的关节软骨细胞凋亡的实验研究[J].中国临床药理学杂志,2014,30(1):30-2.[24]Wu X A,Hu B,Chen H H,et al.Effects of amiloride on apoptosis of articular chondrocytes in rats with osteoarthritis induced by sodium nitroprusside[J].Chin J Clin Pharmacol,2014,30(1):30-2.
[25]Kweon H J.Acid-sensing ion channels(ASICs):therapeutic targets for neurological diseases and their regulation[J].BMB Rep,2013,46(6):295-304.
[2]Lin Y C,Liu Y C,Huang Y Y,et al.High-density expression of Ca2+-permeable ASIC1a channels in NG2 glia of rat hippocampus[J].PLo S One,2010,5(9):e12665.
[3]Baconguis I,Bohlen C J,Goehring A,et al.X-ray structure of acid-sensing ion channel 1-snake toxin complex revealsopen state of a Na+-selective channel[J].Cell,2014,156(4):717-29.
[4]Deval E.Acid-sensing ion channels and nociception in the peripheral and central nervous systems[J].Neuropharmacology,2015,94(7):49-57.
[5]Jahr H,van Driel M,van Osch G J,et al.Identification of acidsensing ion channels in bone[J].Biochem Biophys Res Commun,2005,337(1):349-54.
[6]袁凤来,陈飞虎,黄学应,等.酸敏感离子通道在大鼠佐剂性关节炎关节软骨中的表达[J].中华风湿病学杂志,2008,12(5):321-4.[6]Yuan F L,Chen F H,Huang X Y,et al.Expression of acid-sensing ion channels in articular cartilage of rat adjuvant arthritis.[J].Chin J Rheumatol,2008,12(5):321-4.
[7]Chu X P,Grasing K A.Acid-sensing ion channels contribute to neurotoxicity[J].Transl Stroke Res,2014,5(1):69-78.
[8]Leng T D,Xiong Z G.The pharmacology and therapeutic potential of small molecule inhibitors of acid-sensing ion channels in stroke intervention[J].Acta Pharmacol Sin,2013,34(1):33-8.
[9]Martinez D,Vermeulen M,Trevani A,et al.Extracellular acidosis induces neutrophil activation by a mechanism dependent on activation of phosphatidylinositol 3-kinase/Akt and ERK pathways[J].J Immunol,2006,176(2):1163-71.
[10]Rong C,Chen F H,Jiang S,et al.Inhibition of acid-sensing ion channels by amiloride protects rat articular chondrocytes from acidinduced apoptosis via a mitochondrial-mediated pathway[J].Cell Biol Int,2012,36(7):635-41.
[11]Yuan F L,Chen F H,Lu W G,et al.Acid-sensing ion channel1a mediates acid-induced increases in intracellular calcium in rat articular chondrocytes[J].Mol Cell Biochem,2011,340(1-2):153-9.
[12]江晟,陈飞虎,陈寸知,等.siRNA沉默ASIC1a基因对佐剂性关节炎大鼠关节软骨细胞凋亡的影响研究[J].中国临床药理学与治疗学,2012,17(3):256-62.[12]Jiang S,Chen F H,Chen C Z,et al.Effect of siRNA silencing ASIC1a gene on apoptosis of articular chondrocytes in rats with adjuvant arthritis[J].Chin J Clin Pharmacol Ther,2012,17(3):256-62.
[13]Auberger P.Autophagy.A key mechanism of oncogenesis and resistance in leukemia[J].Blood,2017,129(5):547-52.
[14]张晨晨,唐杰,胡伟,等.酸敏感离子通道1a在酸诱导的大鼠关节软骨细胞自噬的作用及其机制研[J].中国药理学通报,2013,29(8):1092-8.[14]Zhang C C,Tang J,Hu W,et al.Effects of acid-sensing ion channel 1a on acid-induced autophagy of rat articular chondrocytes and its mechanism[J].Chin Pharmacol Bull,2013,29(8):1092-8.
[15]高文凡,陈飞虎,葛金芳,等.钙络合剂BAPTA-AM对胞外酸化诱导大鼠关节软骨细胞自噬作用的影响及其可能机制[J].中国药理学通报,2015,31(5):655-9.[15]Gao W F,Chen F H,Ge J F,et al.Effects of BAPTA-AM on autophagy of rat articular chondrocytes induced by extracellular acidification and its possible mechanism[J].Chin Pharmacol Bull,2015,31(5):655-9.
[16]Boiko N,Kucher V,Eaton B A.Inhibition of neuronal degenerin/epithelial Na+channels by the multiple sclerosis drug 4-aminopyridine[J].J Biol Chem,2013,288(13):9418-27.
[17]Vergo S,Craner M J,Etzensperger R,et al.Acid-sensing ion channel 1 is involved in both axonal injury and demyelination in multiple sclerosis and its animal model[J].Brain,2011,134(Pt2):571-84.
[18]Friese M A,Craner M J,Etzensperger R,et al.Acid-sensing ion channel-1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system[J].Nat Med,2007,13(12):1483-9.
[19]Arun T,Tomassini V,Sbardella E,et al.Targeting ASIC1 in primary progressive multiple sclerosis:evidence of neuroprotection with amiloride[J].Brain,2013,136(Pt 1):106-15.
[20]St rling J.Type 1 diabetes candidate genes linked to pancreatic islet cell inflammation and beta-cell apoptosis[J].Genes,2017,8(2):pii:E72.
[21]Chai S,Li M,Branigan D,et al.Activation of acid-sensing ion channel 1a(ASIC1a)by surface trafficking[J].J Biol Chem,2010,285(17):13002-11.
[22]Duan B,Liu D S,Huang Y,et al.PI3-kinase/Akt pathway-regulated membrane insertion of acid-sensing ion channel 1a underlies BDNF-induced pain hypersensitivity[J].J Neurosci,2012,32(18):6351-63.
[23]Radu B M,Dumitrescu D I,Marin A,et al.Advanced type 1 diabetes is associated with ASIC alterations in mouse lower thoracic dorsal root ganglia neurons[J].Cell Biochem Biophys,2014,68(1):9-23
[24]吴新安,胡波,陈慧慧,等.阿米洛利对硝普钠诱导的骨性关节炎大鼠的关节软骨细胞凋亡的实验研究[J].中国临床药理学杂志,2014,30(1):30-2.[24]Wu X A,Hu B,Chen H H,et al.Effects of amiloride on apoptosis of articular chondrocytes in rats with osteoarthritis induced by sodium nitroprusside[J].Chin J Clin Pharmacol,2014,30(1):30-2.
[25]Kweon H J.Acid-sensing ion channels(ASICs):therapeutic targets for neurological diseases and their regulation[J].BMB Rep,2013,46(6):295-304.