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Figure 1. Modulation of Tat neurotoxicity by MMP-1. A) Mixed human neuronal cultures were exposed to Tat and MMP-1 either alone or in combination. Mitochondrial mem-brane potential was measured 6 h later. Both Tat and MMP-1, when incubated alone, caused toxicity. However, when incubated together, intermediate concentrations of MMP-1 showed a significant decrease in amounts of toxicity compared to either protein alone (*P<0.05). At low or high MMP-1 concentrations, the respective effects seen with Tat or MMP alone seem to predominate, and the protective effect is lost. Toxicity was measured as a loss of mitochondrial potential compared to untreated control cultures. Data represent mean ± SE. B) Mixed human neuronal cultures were exposed to Tat and MMP-1, either alone or in combination, with or without the broad spectrum MMP inhibitor, FN-439. Cell death was measured by uptake of trypan blue 16 h later. When incubated alone, both Tat and MMP-1 caused significant cell death. When incubated together, however, levels of cell death returned to that seen with no treatment or with FN-439 alone (P<0.001). When Tat, MMP-1, and FN-439 were all incubated together, the MMP-1 protective effect was inhibited and toxicity reappeared (P<0.001). FN439 had no effect on the toxicity of MMP-1 or Tat alone. Concentrations: Tat (200 nM), MMP-1 (20 ng/µl), FN439 (0.5 µg/µl). Data represent mean ± SE.
