K(ATP) channel openers protect mesencephalic neurons against MPP+-induced cytotoxicity via inhibition of ROS production.
K(ATP) channel openers protect mesencephalic neurons against MPP+-induced cytotoxicity via inhibition of ROS production.
复制标题
K(ATP) 通道开放剂通过抑制 ROS 产生来保护中脑神经元免受 MPP 诱导的细胞毒性。
DOI：
10.1002/jnr.22213
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发表时间：
2010
影响因子：
4.2
通讯作者：
Hu Gang
中科院分区：
文献类型：
--
作者：
Xie Juan;Duan Lei;Qian Xia;Huang Xu;Ding Jianhua;Hu Gang
Opening of ATP‐sensitive potassium (KATP) channels has been demonstrated to exert significant neuroprotection in in vivo and in vitro models of Parkinson's disease (PD), but the exact mechanism remains unclear. In the present study, various KATPchannel openers (KCOs) sensitive to diverse KATPsubunits were used to clarify the protective role of KATPchannel opening in 1‐methyl‐4‐phenylpyridinium (MPP+)‐induced oxidative stress injury in mouse primary cultured mesencephalic neurons. The results showed that pretreatment with nonselective KCO pinacidil (Pin) or diazoxide (Dia), a KCO sensitive to Kir6.2/SUR1 KATPchannels, protected mesencephalic neurons, especially dopaminergic neurons, against MPP+‐induced injury in a concentration‐dependent manner. However, cromakalim (Cro), an opener of Kir6.1/SUR2 but not Kir6.2/SUR1 KATPchannels, failed to protect against MPP+‐induced cytotoxicity. Furthermore, Pin and Dia but not Cro significantly suppressed the elevation of reactive oxygen species (ROS) triggered by MPP+and prevented the loss of mitochondrial member potential (ΔΨm) and the release of mitochondrial cyotchrome c. Consequently, opening of KATPchannels expressed in neurons could protect primary mesencephalic neurons against MPP+‐induced cytotoxicity via inhibiting ROS overproduction and subsequently ameliorating mitochondrial function. © 2009 Wiley‐Liss, Inc.
