TABLE 1

Influence of inhibitors of nSMase [glutathione in its reduced (GSH) and oxidized forms (GSSH)], cPLA2 (AACOCF3), MAPKs (SB203580, PD98059), and SPT (L-cycloserine, ISP-1) on R(+)-MA—induced C16-ceramide formation

Cells were incubated with R(+)-MA (10 μM) or its vehicle for 4 h in the presence of the test substances (1 h preincubation). Values are comparisons with the vehicle-treated cells (100%) in the absence of test substance. Values are means ± S.E.M. of n = 3 to 4 experiments.

C16-Ceramide
%
Vehicle 100 ± 23
R(+)-MA (10 μM) 192 ± 18
R(+)-MA + GSH (1 mM) 257 ± 26
R(+)-MA + GSSG (1 mM) 272 ± 62
Vehicle 100 ± 6
R(+)-MA (10 μM) 209 ± 15
R(+)-MA + SB203580 (30 μM) 178 ± 30
R(+)-MA + PD98059 (30 μM) 200 ± 19
R(+)-MA + AACOCF3 (15 μM) 293 ± 144
Vehicle 100 ± 27
R(+)-MA (10 μM) 201 ± 10
R(+)-MA + L-cycloserine (1 mM) 223 ± 21
R(+)-MA + ISP-1 (10 μM) 213 ± 26