Long-lasting inhibition of presynaptic metabolism and neurotransmitter release by protein S-nitrosylation.
Long-lasting inhibition of presynaptic metabolism and neurotransmitter release by protein S-nitrosylation.
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通过蛋白质 S-亚硝基化作用持久抑制突触前代谢和神经递质释放。
DOI：
10.1016/j.freeradbiomed.2010.05.032
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发表时间：
2010
影响因子：
7.4
通讯作者：
Mongin,AlexanderA
中科院分区：
文献类型：
--
作者：
Rudkouskaya,Alena;Sim,Vasiliy;Shah,AabhaA;Feustel,PaulJ;Jourd'heuil,David;Mongin,AlexanderA
一氧化氮（NO）和相关的活性氮物质（RNS）在中风和其他神经退行性疾病的病理生理学中起着重要作用。对中风的后果知之甚少的是突触传递的长期抑制。在这项研究中，我们测试的假设，RNS可以产生长期的抑制神经递质的释放通过S-亚硝基化的蛋白质在突触前神经末梢。我们研究了外源性RNS对大鼠脑突触体囊泡和非囊泡L-[3H]谷氨酸释放的影响。NO/RNS供体，如精胺NONOate，MAHMA NONOate，S-亚硝基-L-半胱氨酸和SIN-1，仅抑制谷氨酸释放的囊泡组分，其效力顺序与蛋白质S-亚硝基化水平密切匹配。在RNS供体分解和洗脱后，谷氨酸释放的抑制持续> 1小时，并且与突触体内ATP水平的降低密切相关。后NO处理的突触体巯基还原剂的S-亚硝基化蛋白的总含量降低，但谷氨酸释放和ATP水平的影响不大。相反，后NO应用的糖酵解，丙酮酸，部分挽救神经递质的释放和ATP的生产的最终产品。这些数据表明，RNS抑制突触前代谢和神经递质释放通过不良可逆的糖酵解和线粒体酶，其中之一被确定为甘油醛-3-磷酸脱氢酶的修改。类似的机制可能有助于在体内亚硝化应激期间神经元通信的长期抑制。
Nitric oxide (NO) and related reactive nitrogen species (RNS) play a major role in the pathophysiology of stroke and other neurodegenerative diseases. One of the poorly understood consequences of stroke is a long-lasting inhibition of synaptic transmission. In this study, we tested the hypothesis that RNS can produce long-term inhibition of neurotransmitter release via S-nitrosylation of proteins in presynaptic nerve endings. We examined the effects of exogenous sources of RNS on the vesicular and nonvesicular L-[3H]glutamate release from rat brain synaptosomes. NO/RNS donors, such as spermine NONOate, MAHMA NONOate, S-nitroso-L-cysteine, and SIN-1, inhibited only the vesicular component of glutamate release with an order of potency that closely matched levels of protein S-nitrosylation. Inhibition of glutamate release persisted for >1h after RNS donor decomposition and washout and strongly correlated with decreases in the intrasynaptosomal ATP levels. Post-NO treatment of synaptosomes with thiol-reducing reagents decreased the total content of S-nitrosylated proteins but had little effect on glutamate release and ATP levels. In contrast, post-NO application of the end-product of glycolysis, pyruvate, partially rescued neurotransmitter release and ATP production. These data suggest that RNS suppress presynaptic metabolism and neurotransmitter release via poorly reversible modifications of glycolytic and mitochondrial enzymes, one of which was identified as glyceraldehyde-3-phosphate dehydrogenase. A similar mechanism may contribute to the long-term suppression of neuronal communication during nitrosative stress in vivo.
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DOI：
10.1152/ajpcell.1995.269.3.c739
发表时间：
1995-09
期刊：
The American journal of physiology
影响因子：
--
作者：
C. M. Padgett;A. Whorton
通讯作者：
C. M. Padgett;A. Whorton
影响因子：
3.9
作者：
ARNELLE, DR;STAMLER, JS
通讯作者：
STAMLER, JS
DOI：
10.1016/s0021-9258(18)41847-9
发表时间：
1992-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Stefanie DimmelerS;Friedrich LottspeichQ;Bernhard BriineSV
通讯作者：
Stefanie DimmelerS;Friedrich LottspeichQ;Bernhard BriineSV
DOI：
10.1085/jgp.95.4.591
发表时间：
1990-04
期刊：
The Journal of general physiology
影响因子：
--
作者：
Erecińska M;Dagani F
通讯作者：
Dagani F
低渗休克激活孤立神经末梢的 Ca2 通道
影响因子：
4.2
作者：
A. A. Mongin;S. L. Aksentsev;S. Orlov;S. Konev
通讯作者：
S. Konev