Effects of Vinpocetine on mitochondrial function and neuroprotection in primary cortical neurons

被引:26
|
作者
Tarnok, K. [1 ,3 ]
Kiss, E. [2 ]
Luiten, P. G. M. [3 ,4 ]
Nyakas, C. [3 ,5 ,6 ]
Tihanyi, K.
Schlett, K. [1 ]
Eisel, U. L. M. [3 ]
机构
[1] Eotvos Lorand Univ, Dept Physiol & Neurobiol, H-1117 Budapest, Hungary
[2] Eotvos Lorand Univ, Dept Immunol, H-1117 Budapest, Hungary
[3] Univ Groningen, Dept Mol Neurobiol, Haren, Netherlands
[4] Univ Groningen, Dept Biol Psychiat, Haren, Netherlands
[5] Hungarian Acad Sci, Neuropsychopharmacol Res Unit, Budapest, Hungary
[6] Semmelweis Univ, Budapest, Hungary
关键词
Vinpocetine; Peripheral benzodiazepine receptors; Neuroprotection; Glutamate excitotoxicity; Mitochondrial membrane potential;
D O I
10.1016/j.neuint.2008.08.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Vinpocetine (ethyl apovincaminate), a synthetic derivative of the Vinca minor alkaloid vincamine, is widely used for the treatment of cerebrovascular-related diseases. One of the proposed mechanisms underlying its action is to protect against the cytotoxic effects Of glutamate overexposure. Glutamate excitotoxicity leads to the disregulation of mitochondrial function and neuronal metabolism. As Vinpocetine has a binding affinity to the peripheral-type benzodiazepine receptor (PBR) involved in the mitochondrial transition pore complex, we investigated whether neuroprotection call be at least partially clue to Vinpocetine's effects on PBRs. Neuroprotective effects of PK11195 and Ro5-4864, two drugs With selective and high affinity to PBR, were compared to Vinpocetine in glutamate excitotoxicity assays oil primary cortical neuronal Cultures. Vinpocetine exerted a neuroprotective action in a 1-50 mu M concentration range while PK11195 and Ro5-4864 were only slightly neuroprotective, especially in high (>25 mu M) concentrations. Combined pretreatment of neuronal Cultures with Vinpocetine and PK11195 or Ro5-4864 showed increased neuroprotection in a dose-dependent manner, indicating that the different drugs may have different targets. To test this hypothesis, mitochondrial membrane potential (MMP) Of Cultured neurons Was measured by flow cytometry. 25 mu M Vinpocetine reduced the decrease of mitochondrial inner membrane potential induced by glutamate exposure, but Ro5-4864 ill itself was found to be more potent to block glutamate-evoked changes ill MMP. Combination of Ro5-4864 and Vinpocetine treatment was found to be even more effective. In summary, the present results indicate that the neuroprotective action of vinpocetine in Culture can not be explained by its effect oil neuronal PBRs alone and that additional drug targets are involved. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:289 / 295
页数:7
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