Copper modulates the phenotypic response of activated BV2 microglia through the release of nitric oxide.
Copper modulates the phenotypic response of activated BV2 microglia through the release of nitric oxide.
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DOI：
10.1016/j.niox.2012.07.002
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发表时间：
2012-12-01
期刊：
影响因子：
--
通讯作者：
Gow AJ
中科院分区：
文献类型：
--
作者：
Rossi-George A;Guo CJ;Oakes BL;Gow AJ
小胶质细胞是中枢神经系统的常驻免疫细胞。它们在神经退行性疾病中的持续激活，传统上归因于神经元功能障碍，可能是由于小胶质细胞无法调节一氧化氮（NO）等细胞毒性介质的释放。在神经退行性疾病中，小胶质细胞持续激活，随后释放 NO，相对于铜 (Cu) 等氧化还原过渡金属的积累，促使人们提出这样的假设：铜会通过改变细胞的氧化还原环境来改变 NO 信号传导，并且通过改变 NO 的命运，小胶质细胞将采取不同的表型。我们使用小胶质细胞模型 BV2 来研究 Cu(I) 对 NO 产生和激活的影响，因为它们已被证明具有表型可塑性。我们的结果表明，BV2 小胶质细胞中的 Cu(I) 不会影响细胞活力，并且它对 iNOS mRNA、蛋白质表达和亚硝酸盐释放没有影响。然而，当 LPS 添加到 Cu(I) 处理的培养基中时，亚硝酸盐释放被消除，而 iNOS 表达没有显着改变。这种效应是 Cu(I) 特异性的，在其他非氧化还原金属中未观察到这种效应，表明 Cu(I) 调节 NO 反应性。免疫荧光分析表明，当 Cu(I) 与 LPS 联合给药时，观察到的 BV2 小胶质细胞响应 LPS 的 M1（炎症）表型转变为 M2（适应性）表型。当 iNOS 功能被 1400W 抑制时，不会观察到同样的变化。在本研究中，我们表明 Cu(I) 调节 NO 向介质的释放，而不改变 iNOS 表达，并在 BV2 小胶质细胞中产生表型变化。
Microglia are resident immune cells of the central nervous system. Their persistent activation in neurodegenerative diseases, traditionally attributed to neuronal dysfunction, may be due to a microglial failure to modulate the release of cytotoxic mediators such as nitric oxide (NO). The persistent activation of microglia with the subsequent release of NO vis-á-vis the accumulation of redox transition metals such as copper (Cu) in neurodegenerative diseases, prompted the hypothesis that copper would alter NO signaling by changing the redox environment of the cell and that, by altering the fate of NO, microglia would adopt a different phenotype. We have used the microglial cell model, BV2, to examine the effects of Cu(I) on NO production and activation as they have been shown to be phenotypically plastic. Our results show that cell viability is not affected by Cu(I) in BV2 microglia and that it has no effect on iNOS mRNA, protein expression and nitrite release. However, when LPS is added to Cu(I)-treated medium, nitrite release is abrogated while iNOS expression is not significantly altered. This effect is Cu(I)-specific and it is not observed with other non-redox metals, suggesting that Cu(I) modulates NO reactivity. Immunofluorescence analysis shows that the M1 (inflammatory) phenotype of BV2 microglia observed in response to LPS, is shifted to an M2 (adaptive) phenotype when Cu(I) is administered in combination with LPS. This same shift is not observed when iNOS function is inhibited by 1400W. In the present study we show that Cu(I) modulates the release of NO to the media, without altering iNOS expression, and produces a phenotypic changes in BV2 microglia.
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影响因子：
5.3
作者：
Ponomarev, Eugene D.;Maresz, Katarzyna;Dittel, Bonnie N.
通讯作者：
Dittel, Bonnie N.
DOI：
10.1196/annals.1306.012
发表时间：
2004-01-01
期刊：
REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS
影响因子：
--
作者：
Huang, XD;Moir, RD;Rogers, JT
通讯作者：
Rogers, JT
影响因子：
56.9
作者：
Nimmerjahn, A;Kirchhoff, F;Helmchen, F
通讯作者：
Helmchen, F
影响因子：
25
作者：
Davalos, D;Grutzendler, J;Gan, WB
通讯作者：
Gan, WB
影响因子：
5.4
作者：
FREI, K;SIEPL, C;FONTANA, A
通讯作者：
FONTANA, A