Copper disrupts S-nitrosothiol signaling in activated BV2 microglia.
Copper disrupts S-nitrosothiol signaling in activated BV2 microglia.
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DOI：
10.1016/j.neuint.2016.05.011
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发表时间：
2016-10
影响因子：
4.2
通讯作者：
Guo CJ
中科院分区：
文献类型：
--
作者：
Rossi-George A;Guo CJ
小胶质细胞是中枢神经系统（CNS）的主要免疫细胞，通过分泌包括一氧化氮（NO）在内的免疫介质对病原体和损伤作出快速反应。NO与抗氧化剂谷胱甘肽反应形成S-亚硝基谷胱甘肽（GSNO），这是体内生物NO的主要库。GSNO被GSNO还原酶（GSNOR）降解。最近，我们已经表明，铜（Cu（I））抑制释放的NO在脂多糖（LPS）刺激的BV 2小胶质细胞，并诱导BV 2小胶质细胞获得一个混合的α个人资料与促炎和抗炎特性。由于GSNOR是GSNO代谢中的关键酶，我们试图确定Cu（I）是否影响活化的BV 2小胶质细胞中的GSNOR活性和S-亚硝基硫醇（SNO）积累。我们的研究结果表明，GSNOR蛋白的表达减少了Cu（I）处理LPS刺激的BV 2小胶质细胞。我们的研究结果还显示，尽管GSNOR表达减少，但S-亚硝基硫醇含量减少。这种效应很可能是由于Cu（I）与S-NO键的中心硫醇反应导致SNO降解。在LPS刺激的BV 2小胶质细胞中，1 μM Cu（I）的剂量不影响SNO蛋白的积累，然而，100 μM Cu（I）的剂量抑制SNO蛋白，与S-亚硝基硫醇的抑制一致。这些数据提供了直接的证据表明，Cu（I）破坏S-亚硝基硫醇稳态和NO代谢，因此，提供了新的见解参与小胶质细胞介导的中枢神经系统疾病的机制。
Microglia, the primary resident immune cells of the central nervous system (CNS), respond rapidly to pathogens and injury by secreting immune mediators including nitric oxide (NO). The reaction of NO with the anti-oxidant glutathione forms S-nitrosoglutathione (GSNO), the major pool of biologic NO in the body. GSNO is degraded by GSNO reductase (GSNOR). Recently, we have shown that copper (Cu(I)) inhibits the release of NO in lipopolysaccharide (LPS)-stimulated BV2 microglia and induces BV2 microglia to acquire a mixed a profile with both pro- and anti-inflammatory characteristics. Since GSNOR is the critical enzyme in GSNO metabolism, we sought to determine whether Cu(I) affects GSNOR activity and S-nitrosothiol (SNO) accumulation in activated BV2 microglia. Our results show that GSNOR protein expression is reduced by Cu(I) treatment in LPS-stimulated BV2 microglia. Our results also show a decrease in S-nitrosothiol content despite a reduced GSNOR expression. This effect is most likely due to Cu(I) reacting with the central thiol of the S-NO bond resulting in the degradation of SNO. A dose of 1 μM Cu(I) did not affect SNO protein accumulation in LPS-stimulated BV2 microglia, however, a dose of 100 μM Cu(I) inhibited SNO protein in accordance with inhibition of S-nitrosothiols. These data provide direct evidence that Cu(I) disrupts S-nitrosothiol homeostasis and NO metabolism, and, thus, provide new insights into the mechanisms involved in microglia-mediated-CNS disorders.
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影响因子：
56.9
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Nimmerjahn, A;Kirchhoff, F;Helmchen, F
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