Paradoxical effect of L-arginine: acceleration of endothelial cell senescence.
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.
Scalera
Fortunato
F
Institute of Clinical Pharmacology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany.
Closs
Ellen I
EI
Flick
Eva
E
Martens-Lobenhoffer
Jens
J
Boissel
Jean P
JP
Lendeckel
Uwe
U
Heimburg
Anke
A
Bode-Böger
Stefanie M
SM
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
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