A positively charged alpha-lipoic acid analogue with increased cellular uptake and more potent immunomodulatory activity

Biochemical and Biophysical Research Communications
C K SenL Packer

Abstract

alpha-Lipoic acid (LA) is taken up by cells and reduced to its potent dithiol form, dihydrolipoate(DHLA), much of which is rapidly effluxed out from cells. To improve retention in cells, the LA molecule was modified to confer a positive charge at physiological pH. N,N-dimethyl,N'-2-amidoethyl-lipoate was synthesized. The protonated form of the new molecule is referred to as LA-Plus. The uptake of LA-Plus by human Wurzburg T cells was higher compared to that of LA. Several-fold higher amounts of DHLA-Plus, the corresponding reduced form of LA-Plus, were detected in LA-Plus treated cells compared to the amount of DHLA found in cells treated with LA. At 100 microM, LA did not but LA-Plus inhibited H2O2 induced NF-kappaB activation and NF-kappaB directed IL-2 receptor expression. Both LA and LA-Plus synergised with selenium in inhibiting H2O2 induced NF-kappaB activation. At 150 microM LA-Plus, but not LA, inhibited TNFalpha induced NF-kappaB activation. At 5 microM LA-Plus, but not LA, protected against both spontaneous and etoposide induced apoptosis in rat thymocytes. LA-Plus is thus an improved form of LA with increased therapeutic potential.

References

Sep 1, 1995·Free Radical Biology & Medicine·J BustamanteS Orrenius

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Citations

Mar 5, 2008·The Journal of Alternative and Complementary Medicine : Research on Paradigm, Practice, and Policy·Raxit J JariwallaDaniel Nakamura
Mar 19, 2002·Canadian Journal of Applied Physiology = Revue Canadienne De Physiologie Appliquée·C K Sen
Oct 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·W T SelfT C Stadtman
Nov 16, 2001·Sports Medicine·C K Sen
Apr 27, 2002·Annals of the New York Academy of Sciences·Jiankang LiuBruce N Ames
Aug 2, 2000·The American Journal of Clinical Nutrition·C K Sen, L Packer
Feb 14, 2002·Archives of Biochemistry and Biophysics·Hadi MoiniLester Packer
May 3, 2003·Free Radical Biology & Medicine·Hans L PerssonUlf T Brunk
Jun 10, 2008·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·A ZulkhairiA Zanariyah

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