Mitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+ toxicity in neuronal cells.
Mitochondrial uncoupling protein-2 (UCP2) mediates leptin protection against MPP+ toxicity in neuronal cells.
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DOI：
10.1007/s12640-009-9109-y
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发表时间：
2010-05
影响因子：
3.7
通讯作者：
Ho, Shu-Leong
中科院分区：
文献类型：
--
作者：
Ho, Philip Wing-Lok;Liu, Hui-Fang;Ho, Jessica Wing-Man;Zhang, Wei-Yi;Chu, Andrew Chi-Yuen;Kwok, Ken Hon-Hung;Ge, Xuan;Chan, Koon-Ho;Ramsden, David Boyer;Ho, Shu-Leong
线粒体功能障碍参与神经退行性疾病的发病机制，包括帕金森病（PD）。解偶联蛋白（UCPs）使ATP的产生与线粒体中的生物燃料氧化脱钩，以减少氧化应激。UCP2在脑中表达，并且在各种毒性损伤下具有神经保护作用。我们观察到诱导UCP2的表达瘦素在神经元培养，并假设瘦素可能通过UCP2保存神经元的生存。我们发现，瘦素通过维持ATP水平和线粒体膜电位（MMP）来保护神经元SH-SY5Y细胞的细胞存活，以对抗MPP+毒性（广泛用于实验性帕金森病模型）;这些作用伴随着UCP2表达的增加。瘦素在调节活性氧水平方面没有作用。UCP2表达的稳定敲除降低ATP水平，并消除瘦素对MPP+诱导的线粒体去极化，ATP缺乏和细胞死亡的保护，表明UCP2在介导瘦素对MPP+毒性的神经保护作用中至关重要。有趣的是，UCP2敲除增加了UCP4的表达，但没有UCP5。我们的研究结果表明，瘦素通过维持MPP+诱导的毒性中UCP2介导的MMP和ATP水平来保护细胞存活。
Mitochondrial dysfunction is involved in the pathogenesis of neurodegenerative diseases, including Parkinson’s disease (PD). Uncoupling proteins (UCPs) delink ATP production from biofuel oxidation in mitochondria to reduce oxidative stress. UCP2 is expressed in brain, and has neuroprotective effects under various toxic insults. We observed induction of UCP2 expression by leptin in neuronal cultures, and hypothesize that leptin may preserve neuronal survival via UCP2. We showed that leptin preserved cell survival in neuronal SH-SY5Y cells against MPP+ toxicity (widely used in experimental Parkinsonian models) by maintaining ATP levels and mitochondrial membrane potential (MMP); these effects were accompanied by increased UCP2 expression. Leptin had no effect in modulating reactive oxygen species levels. Stable knockdown of UCP2 expression reduced ATP levels, and abolished leptin protection against MPP+-induced mitochondrial depolarization, ATP deficiency, and cell death, indicating that UCP2 is critical in mediating these neuroprotective effects of leptin against MPP+ toxicity. Interestingly, UCP2 knockdown increased UCP4 expression, but not of UCP5. Our findings show that leptin preserves cell survival by maintaining MMP and ATP levels mediated through UCP2 in MPP+-induced toxicity.
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影响因子：
30.8
作者：
Fleury, C;Neverova, M;Warden, CH
通讯作者：
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影响因子：
4.2
作者：
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