Effect of L-arginine on asymmetric dimethylarginine (ADMA) or homocysteine-accelerated endothelial cell aging.
We investigated here the effect of l-arginine on asymmetric dimethylarginine (ADMA) or homocysteine-accelerated endothelial aging. Endothelial cells were cultured in medium containing 70micromol/L arginine until fourteenth passage. ADMA, dl-homocysteine, and l-arginine were replaced every 48h starting at the fourth passage. ADMA or homocysteine inhibited significantly the population doublings (PD) and accelerated the process of aging. Co-incubation with l-arginine enhanced PD, inhibited senescence associated beta-galactosidase activity, and increased telomerase activity. This effect was associated with an increase in NO synthesis and NO synthase protein expression. Furthermore, l-arginine-induced NO formation was accompanied by a reduction in oxidative stress and an increase in protein expression and enzyme activity of heme oxygenase (HO)-1. The NO synthase inhibitor l-NAME completely abolished the effect of l-arginine on ADMA or homocysteine-accelerated aging. These findings demonstrate that l-arginine prevents the onset of endothelial aging in ADMA or homocysteine-treated cells by increasing NO formation and consequently the induction of HO-1. This might provide a new strategy to delay ADMA or homocysteine-accelerated aging.
Scalera
Fortunato
F
Institute of Clinical Pharmacology, University Hospital Otto-von-Guericke University, Magdeburg, Germany.
Martens-Lobenhoffer
Jens
J
Täger
Michael
M
Bukowska
Alicja
A
Lendeckel
Uwe
U
Bode-Böger
Stefanie M
SM
D000375:Aging; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018384:Oxidative Stress; D019098:Telomerase / Q000378:metabolism; D013997:Time Factors
D006710:Homocysteine; C018524:N,N-dimethylarginine; D001120:Arginine; D019098:Telomerase; D019331:NG-Nitroarginine Methyl Ester