The role of excitotoxic programmed necrosis in acute brain injury.
The role of excitotoxic programmed necrosis in acute brain injury.
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DOI：
10.1016/j.csbj.2015.03.004
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发表时间：
2015
影响因子：
6
通讯作者：
Fujikawa, Denson G.
中科院分区：
文献类型：
--
作者：
Fujikawa, Denson G.
兴奋性毒性涉及当存在过度神经元去极化时，突触前神经末梢和星形胶质细胞谷氨酸摄取的逆转过度释放谷氨酸。N-甲基-d-天冬氨酸（NMDA）受体是谷氨酸受体的一种亚型，在突触后神经元中被激活，打开其受体操纵的阳离子通道以允许Ca 2+内流。Ca 2+内流激活两种酶，钙蛋白酶I和神经元型一氧化氮合酶（nNOS）。钙蛋白酶I激活引起线粒体释放细胞色素c（cyt c）、截短的凋亡诱导因子（tAIF）和核酸内切酶G（endoG），溶酶体释放组织蛋白酶B和D以及DNA酶II，以及质膜Na+-Ca 2+交换剂失活，这增加了细胞内Ca 2+的积累。tAIF参与大规模DNA切割，cyt c可能参与染色质凝聚; endoG产生核小体间DNA切割。其他蛋白质的核作用尚未确定。nNOS形成一氧化氮（NO），与超氧化物（O2−）反应形成过氧亚硝酸盐（ONOO−）。这些自由基破坏细胞膜、细胞内蛋白质和DNA。DNA损伤激活聚（ADP-核糖）聚合酶-1（PARP-1），其产生聚（ADP-核糖）（PAR）聚合物，其离开细胞核并易位到线粒体膜，也释放AIF。聚（ADP-核糖）糖水解酶将PAR聚合物水解成ADP-核糖分子，其易位至质膜，激活美拉汀样瞬时受体电位2（TRPM-2）通道，其打开，允许Ca 2+流入神经元。NADPH氧化酶（NOX 1）通过细胞膜传递电子，产生O2−。这些过程的结果是神经元坏死，这是一种程序性细胞死亡，是成人大脑中所有急性神经元损伤的基础。
Excitotoxicity involves the excessive release of glutamate from presynaptic nerve terminals and from reversal of astrocytic glutamate uptake, when there is excessive neuronal depolarization. N-methyl-d-aspartate (NMDA) receptors, a subtype of glutamate receptor, are activated in postsynaptic neurons, opening their receptor-operated cation channels to allow Ca2 + influx. The Ca2 + influx activates two enzymes, calpain I and neuronal nitric oxide synthase (nNOS). Calpain I activation produces mitochondrial release of cytochrome c (cyt c), truncated apoptosis-inducing factor (tAIF) and endonuclease G (endoG), the lysosomal release of cathepsins B and D and DNase II, and inactivation of the plasma membrane Na+–Ca2 + exchanger, which add to the buildup of intracellular Ca2 +. tAIF is involved in large-scale DNA cleavage and cyt c may be involved in chromatin condensation; endoG produces internucleosomal DNA cleavage. The nuclear actions of the other proteins have not been determined. nNOS forms nitric oxide (NO), which reacts with superoxide (O2−) to form peroxynitrite (ONOO−). These free radicals damage cellular membranes, intracellular proteins and DNA. DNA damage activates poly(ADP-ribose) polymerase-1 (PARP-1), which produces poly(ADP-ribose) (PAR) polymers that exit nuclei and translocate to mitochondrial membranes, also releasing AIF. Poly(ADP-ribose) glycohydrolase hydrolyzes PAR polymers into ADP-ribose molecules, which translocate to plasma membranes, activating melastatin-like transient receptor potential 2 (TRPM-2) channels, which open, allowing Ca2 + influx into neurons. NADPH oxidase (NOX1) transfers electrons across cellular membranes, producing O2−. The result of these processes is neuronal necrosis, which is a programmed cell death that is the basis of all acute neuronal injury in the adult brain.
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DOI：
10.1073/pnas.0606526103
发表时间：
2006-11-28
影响因子：
11.1
作者：
Andrabi, Shaida A.;Kim, No Soo;Dawson, Ted M.
通讯作者：
Dawson, Ted M.
影响因子：
8
作者：
Blenn, C.;Wyrsch, P.;Bader, J.;Bollhalder, M.;Althaus, Felix R.
通讯作者：
Althaus, Felix R.
DOI：
10.2741/3297
发表时间：
2009-01-01
期刊：
Frontiers in bioscience (Landmark edition)
影响因子：
--
作者：
David KK;Andrabi SA;Dawson TM;Dawson VL
通讯作者：
Dawson VL
DOI：
10.1196/annals.1387.006
发表时间：
2007-01-01
期刊：
SODIUM-CALCIUM EXCHANGE AND THE PLASMA MEMBRANE CA2+-ATPASE IN CELL FUNCTION: FIFTH INTERNATIONAL CONFERENCE
影响因子：
--
作者：
Bano, D.;Munarriz, E.;Nicotera, P.
通讯作者：
Nicotera, P.
影响因子：
4.3
作者：
Baritaud, Mathieu;Boujrad, Hanan;Susin, Santos A.
通讯作者：
Susin, Santos A.