Kitahara Tadashi, Li Ha-Sheng, Balaban Carey D
Department of Otolaryngology, University of Pittsburgh School of Medicine, 107 Eye and Ear Institute, 203 Lothrop Street, Pittsburgh, PA 15123, USA.
Hear Res. 2004 Oct;196(1-2):39-48. doi: 10.1016/j.heares.2004.02.002.
Uncoupling proteins (UCPs) are a proton transporter family located in the mitochondrial inner membrane. The molecular expression and activity of UCPs in brown adipose tissue and skeletal muscle are regulated by factors as diverse as chronic overeating and cold exposure, suggesting roles in energy expenditure and heat production. Although UCP2, UCP4 and brain mitochondrial carrier protein-1 (BMCP-1, i.e. UCP5) mRNAs are expressed in the central nervous system, their central function is unknown. This study presents the first evidence on localization and quantitative expression of UCPs in the rat inner ear by real-time PCR and immunohistochemistry. Real-time PCR studies revealed that UCP2 mRNA was expressed in the vestibular and spiral ganglia more abundantly than any other UCP. Neocortex, by contrast, contained UCP2 and UCP4 equally. Notably, UCP3 and UCP4 mRNAs were expressed in inner ear ganglia, but brain UCP3 mRNA expression level was undetectable by simple PCR. Immunohistochemical studies confirmed that both UCP2- and UCP3-like immunoreactivities were detected in vestibular and spiral ganglion cells and co-localized with a mitochondrial marker, MitoFluorGreen. According to previous reports, UCP2 and UCP3 are thermogenic in yeast and brain UCP2 has been suggested to modulate pre- and post-synaptic events by axonal thermogenesis. It has also been reported recently that UCP2 and UCP3 responses to superoxide application may be an antioxidant protective mechanism. Therefore, it is suggested that mitochondrial UCPs (UCP2, UCP3, UCP4) may play both a protective role against oxidative damage and a thermal signaling role in the eighth nerve.
解偶联蛋白（UCPs）是位于线粒体内膜的质子转运体家族。棕色脂肪组织和骨骼肌中UCPs的分子表达和活性受多种因素调节，如长期暴饮暴食和寒冷暴露，这表明它们在能量消耗和产热中发挥作用。尽管UCP2、UCP4和脑线粒体载体蛋白1（BMCP-1，即UCP5）的信使核糖核酸（mRNAs）在中枢神经系统中表达，但其在中枢的功能尚不清楚。本研究通过实时聚合酶链反应（PCR）和免疫组织化学首次提供了大鼠内耳中UCPs定位和定量表达的证据。实时PCR研究显示，UCP2 mRNA在前庭神经节和螺旋神经节中的表达比其他任何UCP都更丰富。相比之下，新皮质中UCP2和UCP4的含量相当。值得注意的是，UCP3和UCP4的mRNAs在内耳神经节中表达，但通过简单PCR无法检测到脑UCP3 mRNA的表达水平。免疫组织化学研究证实，在前庭神经节和螺旋神经节细胞中均检测到UCP2和UCP3样免疫反应性，且与线粒体标记物MitoFluorGreen共定位。根据之前的报道，UCP2和UCP3在酵母中具有产热作用，并且有人提出脑UCP2可通过轴突产热调节突触前和突触后事件。最近也有报道称，UCP2和UCP3对超氧化物的反应可能是一种抗氧化保护机制。因此，有人认为线粒体UCPs（UCP2、UCP3、UCP4）可能在第八对脑神经中既发挥抗氧化损伤的保护作用，又发挥热信号传导作用。
