Opening of microglial K(ATP) channels inhibits rotenone-induced neuroinflammation.
Opening of microglial K(ATP) channels inhibits rotenone-induced neuroinflammation.
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DOI：
10.1111/j.1582-4934.2007.00144.x
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发表时间：
2008-09
影响因子：
5.3
通讯作者：
Hu G
中科院分区：
文献类型：
--
作者：
Zhou F;Yao HH;Wu JY;Ding JH;Sun T;Hu G
由于激活的小胶质细胞 (MG) 是一种早期征兆，通常先于并引发神经元死亡，因此抑制小胶质细胞激活并减少随后的神经毒性可能会带来治疗益处。本研究表明，大鼠原代培养的MG表达KATP通道的Kir6.1和SUR2亚基，这与BV-2小胶质细胞系中表达的相同。经典的 KATP 通道开放剂吡那地尔和选择性线粒体 KATP (mito-KATP) 通道开放剂二氮嗪可阻止鱼藤酮诱导的小胶质细胞激活和促炎因子（肿瘤坏死因子 [TNF]-α 和前列腺素 E2[PGE2]）的产生。并且吡那地尔和二氮嗪的作用被mito-KATP阻滞剂5-羟基癸酸酯(5-HD)逆转，表明mito-KATP通道参与了小胶质细胞活化的调节。此外，潜在机制涉及小胶质细胞中线粒体膜电位的稳定和 p38/c-Jun-N 末端激酶 (JNK) 激活的抑制。此外，体内研究证实，二氮嗪对鱼藤酮具有神经保护作用，并抑制小胶质细胞活化和神经炎症。因此，小胶质细胞线粒体-KATP 通道可能是治疗帕金森病等神经炎症相关退行性疾病的新的前瞻性靶点。
As activated microglia (MG) is an early sign that often precedes and triggers neuronal death, inhibition of microglial activation and reduction of subsequent neurotoxicity may offer therapeutic benefit. The present study demonstrates that rat primary cultured MG expressed Kir6.1 and SUR2 subunits of KATP channel, which was identical to that expressed in BV-2 microglial cell line. The classic KATP channel opener pinacidil and selective mitochondrial KATP (mito-KATP) channel opener diazoxide prevented rotenone-induc microglial activation and production of pro-inflammatory factors (tumour necrosis factor[TNF]-α and prostaglandin E2[PGE2]). And the effects of pinacidil and diazoxide were reversed by mito-KATP blocker 5-hydroxydecanoate (5-HD), indicating that mito-KATP channels participate in the regulation of microglial activation. Moreover, the underlying mechanisms involved the stabilization of mitocho drial membrane potential and inhibition of p38/c-Jun-N-terminal kinase (JNK) activation in microglia. Furthermore, the in vivo study confirmed that diazoxide exhibited neuroprotective effects against rotenone along with the inhibition of microglial activation and neuroinflammation. Thus, microglial mito-KATP channel might be a novel prospective target for the treatment of neuroinflammation-related degenerative disorders such as Parkinson's disease.
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影响因子：
4.7
作者：
Hu, LF;Wang, S;Hu, G
通讯作者：
Hu, G
影响因子：
25
作者：
Liss, B;Haeckel, O;Roeper, J
通讯作者：
Roeper, J
DOI：
10.1097/00004647-200204000-00007
发表时间：
2002-04-01
影响因子：
6.3
作者：
Liu, D;Lu, CB;Mattson, MP
通讯作者：
Mattson, MP
影响因子：
5.3
作者：
Gao, HM;Hong, JS;Liu, B
通讯作者：
Liu, B
DOI：
10.1124/jpet.jpet.105.094987
发表时间：
2006-02-01
影响因子：
3.5
作者：
Hu, J;Lindenberger, K;Wu, J
通讯作者：
Wu, J