Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
Neuroscience. 2013 Nov 12;252:98-108. doi: 10.1016/j.neuroscience.2013.08.002. Epub 2013 Aug 9.
Accumulating evidence suggests that the metabolism of l-arginine, a metabolically versatile amino acid, is critically involved in the aging process. The present study compared the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of l-arginine and its eight down-stream metabolites in the brain stem (pons and medulla) and the cervical spinal cord in 3- (young) and 22- (aged) month-old male Sprague-Dawley rats. Total NOS activity was significantly reduced with age in the spinal cord (but not brain stem), and there were no age-related changes in arginase activity in both regions. Western blot revealed decreased protein expression of endothelial NOS, but not neuronal NOS, with age in both regions. Furthermore, there were significantly decreased l-arginine, glutamate, GABA and spermine levels and increased putrescine and spermidine levels with age in both regions. Although the absolute concentrations of l-arginine and six metabolites were significantly different between the brain stem and spinal cord in both age groups, there were similar clusters between l-arginine and its three main metabolites (l-citrulline, l-ornithine and agmatine) in both regions, which changed as a function of age. These findings, for the first time, demonstrate the regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord. Future research is required to understand the functional significance of these changes and the underlying mechanisms.
越来越多的证据表明，代谢多功能氨基酸 l-精氨酸的代谢与衰老过程密切相关。本研究比较了 3 个月（年轻）和 22 个月（年老）雄性 Sprague-Dawley 大鼠脑干（脑桥和延髓）和颈脊髓中一氧化氮合酶（NOS）和精氨酸酶的活性和蛋白表达，以及 l-精氨酸及其八种下游代谢物的水平。脊髓（而非脑干）中的总 NOS 活性随年龄增长而显著降低，而两个区域中的精氨酸酶活性均无年龄相关性变化。Western blot 显示内皮型 NOS 的蛋白表达随年龄增长而降低，而神经元型 NOS 则没有变化。此外，两个区域中的 l-精氨酸、谷氨酸、GABA 和亚精胺水平随年龄增长而降低，而腐胺和精胺水平随年龄增长而升高。尽管两组大鼠脑干和脊髓中的 l-精氨酸和六种代谢物的绝对浓度存在显著差异，但两个区域中 l-精氨酸及其三种主要代谢物（l-瓜氨酸、l-鸟氨酸和精胺酸）之间存在相似的聚类，且随年龄变化而变化。这些发现首次证明了大鼠脑干和脊髓中精氨酸代谢的区域差异和年龄相关性变化。需要进一步研究以了解这些变化的功能意义和潜在机制。
