A–B. HAEC were pre-treated with AGI-1067 at 10 μM or control (0.1% DMSO) for 1 hour prior to co-treatment with 2 μg/ml LPS for indicated times. Whole-cell lysates were used to determine the levels of total and phospho-ASK1 by Western blot analysis. Relative phosphorylations of ASK1 (p-ASK1:ASK1) were quantified. The The figures are representative data from at least three separate experiments. * P <0.05.
C–D. AGI-1067 prevent LPS-induced dissociation of Trx1, but not 14-3-3, from ASK. HAEC were pre-treated with AGI-1067 at 10 μM or control (0.1% DMSO) for 1 hour prior to co-treatment with 2 μg/ml LPS for indicated times. Cell lysates were immunoprecipitated with anti-Trx1 or anti-14-3-3 antibody followed by Western blot with anti-ASK1 or respective antibodies as indicated. LPS induces release of ASK1 from both Trx1 and 14-3-3. However, AGI1067 blocks the release of ASK1 from Trx1, but not from 14-3-3, consistent with the anti-oxidant effects of AGI-1067. Relative Trx1-and 14-3-3-bound ASK1 (pulldown ASK1:input ASK1) were quantified. TThe figures are representative data from at least three separate experiments. * P <0.05.