Knockdown of uncoupling protein-5 in neuronal SH-SY5Y cells:: Effects on MPP+-induced mitochondrial membrane depolarization, ATP deficiency, and oxidative cytotoxicity
Knockdown of uncoupling protein-5 in neuronal SH-SY5Y cells:: Effects on MPP+-induced mitochondrial membrane depolarization, ATP deficiency, and oxidative cytotoxicity
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DOI：
10.1002/jnr.21034
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发表时间：
2006-11-01
影响因子：
4.2
通讯作者：
Ho, Shu-Leong
中科院分区：
文献类型：
--
作者：
Ho, Philip Wing-Lok;Chu, Andrew Chi-Yuen;Ho, Shu-Leong
解偶联蛋白（UCPs）通过分散线粒体内膜上的质子梯度，将氧化磷酸化与ATP合成解偶联。神经元特异性UCP 5的生理作用是未知的。我们探讨了在正常和MPP+诱导的细胞毒性条件下，人儿茶酚胺能SH-SY 5 Y细胞中UCP 5表达减少对线粒体膜电位（MMP）、氧化应激、ATP水平和细胞活力的影响。UCP 5的表达减少了56%的siRNA相比，scrambled-siRNA控制。UCP 5敲低诱导细胞凋亡，但不影响正常条件下细胞中ATP、氧化应激和MMP的基础水平。然而，UCP 5敲低使MPP+诱导的细胞毒性增加15%，氧化应激水平增加40%，并使MPP+诱导的线粒体去极化部分恢复57%。UCP 2和UCP 4表达不受UCP 5敲低的影响。细胞毒性、氧化应激和MMP修饰的加剧以及MPP+毒性下UCP 5表达的降低表明，UCP 5可能在氧化应激诱导的神经变性的病理学中具有生理学重要性。(c)2006威利-利斯公司
Uncoupling proteins (UCPs) uncouple oxidative phosphorylation from ATP synthesis by dissipating proton gradient across mitochondrial inner membrane. The physiological role of neuronal specific UCP5 is unknown. We explored the effects of reduced UCP5 expression on mitochondrial membrane potential (MMP), oxidative stress, ATP levels, and cell viability, under normal and MPP+-induced cytotoxic conditions, in human catecholaminergic SH-SY5Y cells. UCP5 expression was reduced by 56% by siRNA, compared to scrambled-siRNA controls. UCP5 knockdown induced apoptosis but did not affect basal levels of ATP, oxidative stress and MMP in the cells under normal conditions. However, UCP5 knockdown increased MPP+-induced cytotoxicity by 15% and oxidative stress levels by 40%, and partially restored MPP+-induced mitochondrial depolarization by 57%. UCP2 and UCP4 expression were unaffected by UCP5 knockdown. Exacerbation of cytotoxicity, oxidative stress and modification of MMP with reduced UCP5 expression in the face of MPP+ toxicity suggest that UCP5 might be physiologically important in the pathology of oxidative stress-induced neurodegeneration. (c) 2006 Wiley-Liss, Inc.