Mattiasson Gustav, Shamloo Mehrdad, Gido Gunilla, Mathi Kavitha, Tomasevic Gregor, Yi Saili, Warden Craig H, Castilho Roger F, Melcher Thorsten, Gonzalez-Zulueta Mirella, Nikolich Karoly, Wieloch Tadeusz
Wallenberg Neuroscience Center, BMC A13, 221 84 Lund, Sweden.
Nat Med. 2003 Aug;9(8):1062-8. doi: 10.1038/nm903. Epub 2003 Jul 13.
Whereas uncoupling protein 1 (UCP-1) is clearly involved in thermogenesis, the role of UCP-2 is less clear. Using hybridization, cloning techniques and cDNA array analysis to identify inducible neuroprotective genes, we found that neuronal survival correlates with increased expression of Ucp2. In mice overexpressing human UCP-2, brain damage was diminished after experimental stroke and traumatic brain injury, and neurological recovery was enhanced. In cultured cortical neurons, UCP-2 reduced cell death and inhibited caspase-3 activation induced by oxygen and glucose deprivation. Mild mitochondrial uncoupling by 2,4-dinitrophenol (DNP) reduced neuronal death, and UCP-2 activity was enhanced by palmitic acid in isolated mitochondria. Also in isolated mitochondria, UCP-2 shifted the release of reactive oxygen species from the mitochondrial matrix to the extramitochondrial space. We propose that UCP-2 is an inducible protein that is neuroprotective by activating cellular redox signaling or by inducing mild mitochondrial uncoupling that prevents the release of apoptogenic proteins.
虽然解偶联蛋白1（UCP - 1）显然参与产热，但UCP - 2的作用尚不清楚。我们使用杂交、克隆技术和cDNA阵列分析来鉴定可诱导的神经保护基因，发现神经元存活与Ucp2表达增加相关。在过表达人UCP - 2的小鼠中，实验性中风和创伤性脑损伤后脑损伤减轻，神经功能恢复增强。在培养的皮质神经元中，UCP - 2减少细胞死亡并抑制氧和葡萄糖剥夺诱导的半胱天冬酶 - 3激活。2,4 - 二硝基苯酚（DNP）引起的轻度线粒体解偶联减少神经元死亡，在分离的线粒体中棕榈酸可增强UCP - 2活性。同样在分离的线粒体中，UCP - 2将活性氧从线粒体基质释放转移到线粒体外空间。我们提出UCP - 2是一种可诱导蛋白，通过激活细胞氧化还原信号或诱导轻度线粒体解偶联来防止凋亡蛋白释放，从而发挥神经保护作用。
