The role of reversible oxidative protein modification in regulation of neurotransmitter systems

可逆氧化蛋白修饰在神经递质系统调节中的作用

• 批准号: RGPIN-2014-03694
• 负责人: Wang, JunFeng
• 金额: $ 2.55万
• 依托单位: University of Manitoba
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=587362
• 关键词: role; reversible; oxidative; protein; modification

Reactive oxygen species are produced by oxygen metabolic processes in the cell. Although excessive reactive oxygen species that cause oxidative damage contribute to pathological development in many diseases, the precise role of reactive oxygen species in physiological regulation remains to be determined. The brain constitutes less than 2% of total body weight, but consumes about 20% of total body oxygen. This high oxygen consumption rate leads to a high base level of reactive oxygen species. Those reactive oxygen species can modify amino acids in proteins and affect protein functioning in the brain. Neurotransmitters transport signals from one neuron to another via synapses, which is the essential basis of neuronal functioning. After neurotransmitters are synthesized in neurons, vesicular neurotransmitter transporters pack them into synaptic vesicles and later release them, targeting receptors in other neurons. These transporters are essential components of chemical transmission between neurons. Recently we found that reactive oxygen species can cause oxidative modification of these vesicular neurotransmitter transporters, suggesting that oxidative modification of synaptic proteins may contribute to regulation of neurotransmitter systems. From this finding, we can hypothesize that oxidative modification of vesicular neurotransmitter transporters by reactive oxygen species may have a part to play in transporter activity. We will now focus on studying if this oxidative modification does indeed have an important role in regulation of transporter activity. We will also identify the individual amino acids in those transporters that can be modified by reactive oxygen species. Our research program allows us to systematically analyze the potential role of reactive oxygen species in regulation of neurotransmission and in brain functioning. This proposed research will significantly increase our understanding of reactive oxygen species in regulating neuronal function and will particularly facilitate a greater understanding of the nature of reactive oxygen specie signaling in physiological functioning of the brain.

活性氧是由细胞内的氧代谢过程产生的。虽然过多的活性氧引起的氧化损伤有助于许多疾病的病理发展，但活性氧在生理调节中的确切作用仍有待确定。大脑占全身重量不到2%，但消耗全身氧气的20%左右。这种高耗氧率导致了活性氧的高基础水平。这些活性氧可以修饰蛋白质中的氨基酸并影响大脑中蛋白质的功能。