Regional variations and age-related changes in arginine metabolism in the rat brain stem and spinal cord.
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.
Department of Anatomy, University of Otago, Dunedin, New Zealand; Brain Health Research Centre, University of Otago, Dunedin, New Zealand.
Y
Y
Jing
M S
MS
Fleete
N D
ND
Collie
H
H
Zhang
P
P
Liu
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000378:metabolism*; D015153:Blotting, Western; D001933:Brain Stem / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism*
D001120:Arginine
ADC; ANOVA; ASL; ASS; HPLC; LC/MS; NADHP-d; NO; NOS; ODC; PUT; SPD; aging; analysis of variance; arginine decarboxylase; argininosuccinate lyase; argininosuccinate synthetase; brain stem; eNOS; endothelial nitric oxide synthase; high-performance liquid chromatography; iNOS; inducible nitric oxide synthase; l-arginine; liquid chromatography/mass spectrometry; nNOS; neuronal nitric oxide synthase; nicotinamide adenine dinucleotide phosphate-diaphorase; nitric oxide; nitric oxide synthase; ornithine decarboxylase; polyamines; putrescine; spermidine; spinal cord