title: Paradoxical effect of L-arginine: acceleration of endothelial cell senescence.
abstract: We have recently shown that inhibition of nitric oxide (NO) synthesis by asymmetrical dimethylarginine (ADMA) accelerated endothelial cell (EC) senescence which was prevented by coincubation with L-arginine; however the effect of long-term treatment of l-arginine alone on senescence of ECs have not been investigated. Human ECs were cultured in medium containing different concentrations of L-arginine until senescence. L-Arginine paradoxically accelerated senescence indicated by inhibiting telomerase activity. Moreover, L-arginine decreased NO metabolites, increased peroxynitrite, and 8-iso-prostaglandin F(2alpha) formation. In old cells, the mRNA expression of human amino acid transporter (hCAT)2B, the activity and protein expression of arginase II were upregulated indicated by enhanced urea, L-ornithine, and L-arginine consumption. Inhibition of arginase activity, or transfection with arginase II siRNA prevented L-arginine-accelerated senescence. The most possible explanation for the paradoxical acceleration of senescence by L-arginine so far may be the translational and posttranslational activation of arginase II.
authors: Institute of Clinical Pharmacology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
authors: Fortunato
authors: F
authors: Scalera
authors: Ellen I
authors: EI
authors: Closs
authors: Eva
authors: E
authors: Flick
authors: Jens
authors: J
authors: Martens-Lobenhoffer
authors: Jean P
authors: JP
authors: Boissel
authors: Uwe
authors: U
authors: Lendeckel
authors: Anke
authors: A
authors: Heimburg
authors: Stefanie M
authors: SM
authors: Bode-Böger
mesh_terms: D001119:Arginase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D027201:Cationic Amino Acid Transporter 1 / Q000096:biosynthesis; D027202:Cationic Amino Acid Transporter 2 / Q000096:biosynthesis; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress
chemical_list: D027201:Cationic Amino Acid Transporter 1; D027202:Cationic Amino Acid Transporter 2; C420825:SLC7A1 protein, human; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine; C477631:ARG2 protein, human; D001119:Arginase