EFFECT OF ALPHA-LIPOIC ACID ON THE SENSITIVITY OF TRANSFORMED FIBROBLASTS TO LYSIS BY NATURAL KILLER CELLS.
COMPARISON WITH NAC ACTION
N. A. Filatova, K. M. Kirpichnikova, E. A, Vahromova, I. A. Gamaley 1
Institute of Cytology RAS, St. Petersburg;
1 e-mail: igamaley@mail.cytspb.rssi.ru
The purpose of this study was to compare the effects of two antioxidants, alpha-lipoic acid (ALA) and N-acetylcysteine (NAC) on the sensitivity of 3T3-SV40
fibroblasts to lytic activity of natural killer (NK) cells. ALA (1.25 mM) reduced significantly the fibroblast sensitivity in several hours, whereas NAC (10 mM) did not
change it. Subsequent removal of the antioxidants from the cultivation medium resulted in gradual recovery of the sensitivity in the case of ALA and in, complete loss
of it in the case of NAC. Inactivation of gelatinase MMP-2 (matrix metalloproteinase) using pretreatment of the cells with the inhibitor of MMP, G6001, or specific
antibodies to MMP-2 or MMP-9 resulted in decrease of 3T3-SV40 sensitivity to NK cells activity. This effect was similar to that of ALA, not to the NAC one.
Pretreatment of NK cells with G6001 did not influence their lytic activity. The results obtained demonstrate that the direct antioxidant, NAC (having reduced thiol
groups), and the indirect one, ALA (reducing thiol groups and acting as a direct antioxidant only inside the cell) activate principally different intracellular signal
pathways. However, both NAC and ALA pathway includes inactivation of MMP-2.
Key words: alpha-lipoic acid, N-acetylcysteine, 3T3-SV40 fibroblast, cytotoxic activity, natural killer cells, matrix metalloproteinases
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