Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation
Uncoupling protein 2, in vivo distribution, induction upon oxidative stress, and evidence for translational regulation
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DOI：
10.1074/jbc.m006938200
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发表时间：
2001-03-23
影响因子：
4.8
通讯作者：
Miroux, B
中科院分区：
文献类型：
--
作者：
Pecqueur, C;Alves-Guerra, MC;Miroux, B
解偶联蛋白 2 (UCP2) 属于线粒体阴离子载体家族，在重组酵母线粒体中表达时，可部分解偶联 ATP 合成中的呼吸作用。我们生成了针对人 UCP2 的高度敏感的多克隆抗体。在野生型和 ucp2(-/-) 小鼠之间比较其对线粒体蛋白的反应性，从而明确识别 UCP2。我们在脾、肺、胃和白色脂肪组织中检测到了 UCP2。在心脏、骨骼肌、肝脏和棕色脂肪组织中未检测到 UCP2。脾脏线粒体中UCP2的水平不到棕色脂肪组织线粒体中UCP1水平的1%。饥饿和 LPS 治疗使肺和胃中的 UCP2 水平增加了 12 倍，这支持了 UCP2 对氧化应激情况做出反应的假设。 UCP2 表达的刺激发生时 UCP2 mRNA 水平没有任何变化。这是通过 UCP2 mRNA 的翻译调节来解释的。我们已经表明，位于 ucp2 基因外显子二的上游开放阅读框强烈抑制该蛋白质的表达。 ucp2基因的这种进一步水平的调节提供了一种机制，通过该机制可以在应激条件下强烈且快速地诱导表达。
Uncoupling protein 2 (UCP2) belongs to the mitochondrial anion carrier family and partially uncouples respiration from ATP synthesis when expressed in recombinant yeast mitochondria. We generated a highly sensitive polyclonal antibody against human UCP2. Its reactivity toward mitochondrial proteins was compared between wild type and ucp2(-/-) mice, leading to non-ambiguous identification of UCP2. We detected UCP2 in spleen, lung, stomach, and white adipose tissue. No UCP2 was detected in heart, skeletal muscle, liver, and brown adipose tissue. The level of UCP2 in spleen mitochondria is less than 1% of the level of UCP1 in brown adipose tissue mitochondria. Starvation and LPS treatments increase UCP2 level up to 12 times in lung and stomach, which supports the hypothesis that UCP2 responds to oxidative stress situations. Stimulation of the UCP2 expression occurs without any change in UCP2 mRNA levels. This is explained by translational regulation of the UCP2 mRNA, We have shown that an upstream open reading frame located in exon two of the ucp2 gene strongly inhibits the expression of the protein. This further level of regulation of the ucp2 gene provides a mechanism by which expression can be strongly and rapidly induced under stress conditions.