Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold
Uncoupling protein 2 (UCP2) lowers alcohol sensitivity and pain threshold
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DOI：
10.1016/s0006-2952(02)01167-x
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发表时间：
2002-08-01
影响因子：
5.8
通讯作者：
Horvath, TL
中科院分区：
文献类型：
--
作者：
Horvath, B;Spies, C;Horvath, TL
滥用乙醇是医学上的一个主要风险因素，部分原因是它对中枢神经系统的活动产生广泛影响，包括行为，疼痛和温度感觉。解偶联蛋白2（UCP2）是一种线粒体质子载体，调节细胞能量稳态。UCP2在基底前脑区轴突和轴突终末的线粒体中表达，表明UCP2可能参与调节乙醇引起的复杂神经元反应。我们采用了一种范式，其中急性暴露于乙醇诱导耐受性和改变疼痛和温度感觉。在UCP2过表达小鼠中，与野生型动物相比，对乙醇的敏感性降低，而UCP2敲除小鼠对乙醇的敏感性增加。此外，UCP2的表达与乙醇引起的疼痛和温度感觉的损害呈负相关。两者合计，这些结果表明，UCP2，线粒体解偶联蛋白先前与外周能量消耗，参与调解急性乙醇暴露对中枢神经系统。急性饮酒后UCP2激活的增强可能会减少从中毒中恢复的时间，而UCP2抑制可能会降低对乙醇的耐受性。(C)2002年爱思唯尔科技有限公司All rights reserved.
Abuse of ethanol is a major risk factor in medicine, in part because of its widespread effect on the activity of the central nervous system, including behavior, pain, and temperature sensation. Uncoupling protein 2 (UCP2) is a mitochondrial protonophore that regulates cellular energy homeostasis. Its expression in mitochondria of axons and axon terminals of basal forebrain areas suggests that UCP2 may be involved in the regulation of complex neuronal responses to ethanol. We employed a paradigm in which acute exposure to ethanol induces tolerance and altered pain and temperature sensation. In UCP2 overexpressing mice, sensitivity to ethanol was decreased compared to that of wild-type animals, while UCP2 knockouts had increased ethanol sensitivity. In addition, UCP2 expression was inversely correlated with the impairment of pain and temperature sensation induced by ethanol. Taken together, these results indicate that UCP2, a mitochondrial uncoupling protein previously associated with peripheral energy expenditure, is involved in the mediation of acute ethanol exposure on the central nervous system. Enhancement of UCP2 activation after acute alcohol consumption might decrease the time of recovery from intoxication, whereas UCP2 inhibition might decrease the tolerance to ethanol. (C) 2002 Elsevier Science Inc. All rights reserved.