Paradoxical effect of l

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• 作者：Fortunato Scalera ; Ellen I. Closs ; Eva Flick ; Jens Martens-Lobenhoffer ; Jean P. Boissel ; Uwe Lendeckel ; Anke Heimburg ; Stefanie M. Bode-Bö ; ger
• 关键词：l-Arginine ; Senescence ; Telomerase ; Arginase ; Nitric oxide ; Oxidative stress ; Human cationic amino acid transporter
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：4 September 2009
• 年：2009
• 卷：386
• 期：4
• 页码：650-655
• 全文大小：298 K

文摘

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_2α 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.