AQP4与星形胶质细胞胀亡之间的关系
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摘要
细胞胀亡是不同于细胞凋亡的一种死亡方式,主要是因为细胞内ATP合成障碍,胞膜离子泵功能丧失,导致水及离子进入细胞内,引起细胞器及细胞肿胀,最终细胞死亡。有研究发现缺血缺氧状态下星形胶质细胞的死亡属于胀亡。AQP4是大脑内重要的水通道蛋白之一,主要在星形胶质细胞的足突表达,其主要作用为通过对水的转运,维持细胞内外水平衡。细胞胀亡与水通道的功能有关,星形胶质细胞的胀亡也与AQP4有密切关系,在缺血缺氧的情况下,星形胶质细胞的AQP4表达会出现上调或下调,从而导致星形胶质细胞内外水平衡被破坏,引起星形胶质细胞肿胀,最终出现细胞胀亡。
Oncosis is one kind of cell death associated with intracellular ATP synthesis disorder which is different from apoptosis. In the oncosis pathway, the membrane ion pump function is impaired, leading to cell swelling, ultimately cell death. Some study suggested that the death of astrocytes in ischemia and hypoxia might be oncosis. AQP4, one of the important aquaporins in brain, a small nomoner mainly express in astrocytes foot processes, plays an important role in the water homeostasis of the brain by transportering water. Oncosis is closely associated with aquaporins which is related with astrocytes. In the case of ischemia and hypoxia, the expression of AQP4 would be up-regulated or down-regulated which might contribute the destruction of water balance, causing swelling of the astrocytes, ultimately oncosis.
Oncosis is one kind of cell death associated with intracellular ATP synthesis disorder which is different from apoptosis. In the oncosis pathway, the membrane ion pump function is impaired, leading to cell swelling, ultimately cell death. Some study suggested that the death of astrocytes in ischemia and hypoxia might be oncosis. AQP4, one of the important aquaporins in brain, a small nomoner mainly express in astrocytes foot processes, plays an important role in the water homeostasis of the brain by transportering water. Oncosis is closely associated with aquaporins which is related with astrocytes. In the case of ischemia and hypoxia, the expression of AQP4 would be up-regulated or down-regulated which might contribute the destruction of water balance, causing swelling of the astrocytes, ultimately oncosis.
引文
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[25]Yang B,Zador Z,Verkman A.S.Glial cell aquaporin-4overexpres-sion in transgenic mice accelerates cytotoxic brain swelling[J].J Biol Chem,2008,283(22):15280-15286.
[26]Meng S,Qiao M,Lin L,et al.Correspondence of AQP4expression and hypoxic–ischaemic brain oedema monitored by magnetic reso-nance imaging in the immature and juvenile rat[J].Eur J Neurosci,2004,19(8):2261-2269.
[27]Yamamoto N,Sobue K,Miyachi T,et al.Differential regulation ofaquaporin expression in astrocytes by protein kinase C[J].Brain Res Mol Brain Res,2001,95(1-2):110-116.
[28]Lee M,Lee S.J,Choi H.J,et al.Regulation of AQP4protein expres-sion in rat brain astrocytes:role of P2X7receptor activation[J].Brain Res,2008,1195:1-11.
[29]Kaur C,Sivakumar V,Zhang Y,et al.Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum[J].Glia,2006,54(8):826-839.
[30]Taniguchi M,Yamashita T,Kumura E,et al.Induction of aquaporin-4water channel mRNA after focal cerebral ischemia in rat[J].Brain Res Mol Brain Res,2000,78(1-2):131-137.
[2]Trump B.F,Berezesky I.K,Chang S.H,et al.The pathways of cell death:oncosis,apoptosis and necrosis[J].Toxicol Pathol,1997,25(1):82-88.
[3]曹旭,褚晓凡.细胞胀亡的研究进展[J].中国病理生理杂志,2009,25(12):2473-2477.
[4]Mills E.M,Xu D,Fergusson M.M,et al.Regulation of cellular oncosis by uncoupling protein2[J].J Biol Chem,2002,277(30):27385-27392.
[5]Ma F,Zhang C,Prasad K.V,et al.Molecular cloning of porimin,a nov-el cell surface receptor mediating oncotic cell death[J].Proc Natl Acad Sci USA,2001,98(17):9778-9783.
[6]Buja L.M,Vela D.Cardiomyocyte death and renewal in the normal and diseased heart[J].Cardiovasc Pathol,2008,17(6):349-374.
[7]Chu X,Qi C,Zou L,et al.Intraluminal suture occlusion and ligation of the distal branch of internal carotid artery:An improved rat model of focal cerebral ischemia-reperfusion[J].J Neurosci Methods,2008,168(1):1-7.
[8]Cornelissen M,Thierens H,De Ridder L.Interphase death in human peripheral blood lymphocytes after moderate and high doses of low and high LET radiation:an electron microscopic approach[J].Anti-cancer Res,2002,22(1A):241-245.
[9]Crisby M,Kallin B,Thyberg J,et al.Cell death in human atheroscle-rotic plaques involves both oncosis and apoptosis[J].Atherosclerosis,1997,130(1-2):17-27.
[10]Ohno M,Takemura G,Ohno A,et al.Apoptotic myocytes in infarct area in rabbithearts may be oncotic myocytes with DNA fragmenta-tion[J].Circulation,1998,98(14):1422-1430.
[11]Chu XF,Fu XJ,Zou LY,et al.Oncosis,the possible cell death pathway in astrocytes after focal cerebral ischemia[J].Brain Res,2007,1149:157-164.
[12]Aschner M.Astrocytic functions and physiological reactions to in-jury:the potential to induce and/or exacerbate neuronal dysfunction-A forum position paper[J].Neurotoxicology,1998,19(1):7-17,dis-cussion37-38.
[13]Tsacopoulos M,Magistretti P.J.Metabolic coupling between glia and neurons[J].J Neurosci,1996,16(3):877-885.
[14]Leis J.A,Bekar L.K,Walz W.Potassium homeostasis in the ischemic brain[J].Glia,2005,50(4):407-416.
[15]Petito C.K,Olarte J.P,Robert B,et al.Selective glial vulnerability following transient global ischemia in rat brain[J].J Neuropathol Exp Neurol,1998,57(3):231-238.
[16]Yu A.C.H,Wong H.K,Yung H.M,et al.Ischemia-induced apoptosis in primary culture of astrocytes[J].Glia,2001,35(2):121-130.
[17]Ito U,Hanyu S,Hakamata Y,et al.Ultrastructure of astrocytes asso-ciated with selective neuronal death of cerebral cortex after repeated ischemia[J].Acta Neurochir Suppl,1997,70:46-49.
[18]付学军,褚晓凡,亓传洁.胀亡-持续性局灶性脑缺血星形胶质细胞的死亡方式[J].中华神经医学杂志,2005,4(10):979-982.
[19]Cao X,Zhang Y,Zou L,et al.Persistent oxygen-glucose deprivation induces astrocytic death through two different pathways and cal-pain-mediated proteolysis of cytoskeletal proteins during astrocytic oncosis[J].Neurosci Lett,2010,479(2):118-122.
[20]Verkman AS.More than just water channels:unexpected cellular roles of aquaporins[J].J Cell Sci,2005,118:3225-3232.
[21]Rash JE,Yasumura T,Hudson CS,et al.Direct immunogold labeling of aquaporin-4in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord[J].Proc Natl Acad Sci U S A,1998,95(20):11981-11986.
[22]Klatzo I.Evolution of brain edema concepts[J].Acta Neurochir Sup-pl(Wien),1994,60:3-6.
[23]Manley GT,Fujimura M,Ma T,et al.Aquaporin-4deletion in mice reduces brain edema after acute water intoxication and ischemic stroke[J].Nat Med,2000,6(2):159-163.
[24]Amiry-Moghaddam M,Otsuka T,Hurn PD,et al.An alpha-syntrophin-dependent pool of AQP4in astroglial end-feet confers bidirectional water flow between blood and brain[J].Proc Natl Acad Sci USA,2003,100(4):2106-2111.
[25]Yang B,Zador Z,Verkman A.S.Glial cell aquaporin-4overexpres-sion in transgenic mice accelerates cytotoxic brain swelling[J].J Biol Chem,2008,283(22):15280-15286.
[26]Meng S,Qiao M,Lin L,et al.Correspondence of AQP4expression and hypoxic–ischaemic brain oedema monitored by magnetic reso-nance imaging in the immature and juvenile rat[J].Eur J Neurosci,2004,19(8):2261-2269.
[27]Yamamoto N,Sobue K,Miyachi T,et al.Differential regulation ofaquaporin expression in astrocytes by protein kinase C[J].Brain Res Mol Brain Res,2001,95(1-2):110-116.
[28]Lee M,Lee S.J,Choi H.J,et al.Regulation of AQP4protein expres-sion in rat brain astrocytes:role of P2X7receptor activation[J].Brain Res,2008,1195:1-11.
[29]Kaur C,Sivakumar V,Zhang Y,et al.Hypoxia-induced astrocytic reaction and increased vascular permeability in the rat cerebellum[J].Glia,2006,54(8):826-839.
[30]Taniguchi M,Yamashita T,Kumura E,et al.Induction of aquaporin-4water channel mRNA after focal cerebral ischemia in rat[J].Brain Res Mol Brain Res,2000,78(1-2):131-137.