Cysteine, histidine and glycine exhibit anti-inflammatory effects in human coronary arterial endothelial cells.

The activation of nuclear factor-kappa B (NF-κB) in vascular endothelial cells may be involved in vascular pathogeneses such as vasculitis or atherosclerosis. Recently, it has been reported that some amino acids exhibit anti-inflammatory effects. We investigated the inhibitory effects of a panel of amino acids on cytokine production or expression of adhesion molecules that are involved in inflammatory diseases in various cell types. The activation of NF-κB was determined in human coronary arterial endothelial cells (HCAECs) because NF-κB modulates the production of many cytokines and the expression of adhesion molecules. We examined the inhibitory effects of the amino acids cysteine, histidine and glycine on the induction of NF-κB activation, expression of CD62E (E-selectin) and the production of interleukin (IL)-6 in HCAECs stimulated with tumour necrosis factor (TNF)-α. Cysteine, histidine and glycine significantly reduced NF-κB activation and inhibitor κBα (IκBα) degradation in HCAECs stimulated with TNF-α. Additionally, all the amino acids inhibited the expression of E-selectin and the production of IL-6 in HCAECs, and the effects of cysteine were the most significant. Our results show that glycine, histidine and cysteine can inhibit NF-κB activation, IκBα degradation, CD62E expression and IL-6 production in HCAECs, suggesting that these amino acids may exhibit anti-inflammatory effects during endothelial inflammation.

L-arginine-nitric oxide pathway and chronic nephropathy in aged rats.

Effects of aging and dietary protein on the L-arginine-nitric oxide (Arg-NO) pathway and the progress of chronic nephropathy were examined. At 6-7 months of age, 10 male Fischer 344 rats were fed a 23% protein diet until 24 or 25 months of age, and another 10 were fed a 12% protein diet until that age. Twenty male Fischer 344 rats that were fed the 23% protein diet from 6 to 8 months of age were used as a control. Urinary excretion of nitrite/nitrate (NOx) at the age of 24 months in the 23% protein group was remarkably decreased, whereas in the 12% protein group, urinary NOx remained comparable to that of the control. Histological examination revealed that chronic nephropathy was highly progressive in the 23% protein group, accompanied by lowered renal function, but these changes were obviously suppressed in the 12% protein group. These results suggest that an age-related decrease in the synthesis of NO could be associated with the progress of chronic nephropathy.

Effects of dietary protein restriction on nitrogen balance and cardiovascular functions in aged rats.

Effects of aging and dietary protein restriction on nitrogen balance and cardiovascular functions were examined. Male Fischer 344 rats 6-7 months old were fed ad libitum until 24 or 25 months old with either a 12% or a 23% protein diet, respectively. The nitrogen balance measured at the age of 24 months old demonstrated a significant difference between the two groups: the group with the 23% protein diet had a negative balance, while the group with the 12% protein diet had a positive balance. Endothelium-dependent relaxation with acetylcholine of the thoracic aortas was impaired by age but to a lesser extent to the protein-restricted animals. In addition, increased ability of platelet aggregation according to aging was also significantly suppressed by protein restriction. These observations demonstrate that protein restriction delays the aging effects of nitrogen loss and reduced cardiovascular function.