Uncoupling protein-2 attenuates palmitoleate protection against the cytotoxic production of mitochondrial reactive oxygen species in INS-1E insulinoma cells.
Uncoupling protein-2 attenuates palmitoleate protection against the cytotoxic production of mitochondrial reactive oxygen species in INS-1E insulinoma cells.
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DOI：
10.1016/j.redox.2014.11.009
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发表时间：
2015
期刊：
影响因子：
11.4
通讯作者：
Affourtit, Charles
中科院分区：
文献类型：
--
作者：
Barlow, Jonathan;Jensen, Verena Hirschberg;Affourtit, Charles
关键词：
高葡萄糖和脂肪酸水平损害胰腺β细胞功能。我们最近发现，棕榈酸酯诱导的INS-1 E胰岛素瘤细胞损失与活性氧（ROS）产生增加有关，因为这两种毒性作用都被棕榈酸酯阻止。在这里，我们表明，棕榈酸酯诱导的ROS主要是线粒体：MitoSOX的氧化，一种靶向超氧化物探针，增加棕榈酸酯，而氧化的等效非靶向探针不受影响。此外，线粒体呼吸抑制与抗霉素A刺激棕榈酸诱导的MitoSOX氧化。我们还表明，棕榈酸酯不会改变线粒体解偶联蛋白-2（UCP 2）的水平，并且UCP 2敲低不会影响棕榈酸酯诱导的MitoSOX氧化。棕榈酸酯不影响INS-1 E细胞± UCP 2中的MitoSOX氧化，并在很大程度上防止棕榈酸酯诱导的作用。重要的是，UCP 2敲低放大了棕榈酸酯对棕榈酸酯诱导的ROS的预防作用。一致地，棕榈酸酯和棕榈油酸酯的活力作用在细胞± UCP 2之间是相似的，但是UCP 2敲低显著增强了棕榈油酸酯对高葡萄糖下棕榈酸酯诱导的细胞损失的保护。我们的结论是，UCP 2既不介导棕榈酸诱导的线粒体ROS的产生和相关的细胞损失，也不保护这些有害的影响。相反，UCP 2抑制棕榈酸酯对棕榈酸酯毒性的保护。棕榈酸暴露诱导INS-1 E细胞线粒体超氧化物。线粒体超氧化物与INS-1 E细胞数量呈负相关。棕榈酸盐不会改变INS-1 E细胞中解偶联蛋白-2（UCP 2）的水平。UCP 2不影响棕榈酸诱导的线粒体超氧化物或INS-1 E细胞损失。UCP 2抑制棕榈酸酯对棕榈酸酯毒性的保护作用。
High glucose and fatty acid levels impair pancreatic beta cell function. We have recently shown that palmitate-induced loss of INS-1E insulinoma cells is related to increased reactive oxygen species (ROS) production as both toxic effects are prevented by palmitoleate. Here we show that palmitate-induced ROS are mostly mitochondrial: oxidation of MitoSOX, a mitochondria-targeted superoxide probe, is increased by palmitate, whilst oxidation of the equivalent non-targeted probe is unaffected. Moreover, mitochondrial respiratory inhibition with antimycin A stimulates palmitate-induced MitoSOX oxidation. We also show that palmitate does not change the level of mitochondrial uncoupling protein-2 (UCP2) and that UCP2 knockdown does not affect palmitate-induced MitoSOX oxidation. Palmitoleate does not influence MitoSOX oxidation in INS-1E cells ±UCP2 and largely prevents the palmitate-induced effects. Importantly, UCP2 knockdown amplifies the preventive effect of palmitoleate on palmitate-induced ROS. Consistently, viability effects of palmitate and palmitoleate are similar between cells ±UCP2, but UCP2 knockdown significantly augments the palmitoleate protection against palmitate-induced cell loss at high glucose. We conclude that UCP2 neither mediates palmitate-induced mitochondrial ROS generation and the associated cell loss, nor protects against these deleterious effects. Instead, UCP2 dampens palmitoleate protection against palmitate toxicity. Palmitate exposure induces mitochondrial superoxide in INS-1E cells. Mitochondrial superoxide correlates inversely with INS-1E cell number. Palmitate does not change uncoupling protein-2 (UCP2) level in INS-1E cells. UCP2 does not affect palmitate-induced mitochondrial superoxide or INS-1E cell loss. UCP2 dampens palmitoleate protection against palmitate toxicity.
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影响因子：
3.8
作者：
Pi J;Zhang Q;Fu J;Woods CG;Hou Y;Corkey BE;Collins S;Andersen ME
通讯作者：
Andersen ME
影响因子：
7.4
作者：
Circu, Magdalena L.;Aw, Tak Yee
通讯作者：
Aw, Tak Yee
影响因子：
7.7
作者：
Pi, Jingbo;Bai, Yushi;Collins, Sheila
通讯作者：
Collins, Sheila
影响因子：
30.8
作者：
Fleury, C;Neverova, M;Warden, CH
通讯作者：
Warden, CH
DOI：
10.1073/pnas.0710434105
发表时间：
2008-08-19
影响因子：
11.1
作者：
Diao, Jingyu;Allister, Emma M.;Wheeler, Michael B.
通讯作者：
Wheeler, Michael B.