05);牛磺酸治疗组大鼠心肌中各时相点的Fas、Caspase-8、Caspase-3蛋白水平及Caspase-3活性较烧伤组均有显著性降低(P<0.05)。结论牛磺酸对严重烧伤大鼠心肌中Fas、Caspase-8、Caspase-3蛋白的表达及Caspase-3活性升高均有较好的拮抗作用。
AIM:

To study the effect of gelatinases (especially MMP-9) on migration of tissue inhibitor of metalloproteinase (TIMP-1) overexpressing hepatoma cells. METHODS: Wild type HepG2 cells, cells stably transfected with TIMP-1 and TIMP-1 antagonist (MMP-9-H401A, a catalytically inactive matrix metalloproteinase (MMP) GDC-0199 which still binds and neutralizes TIMP-1) were incubated in Boyden chambers either with or without Galardin (a synthetic inhibitor of MMP-1, -2, -3, -8, -9) or a specific inhibitor of gelatinases. RESULTS: Compared to wild type HepG2 cells, the cells overexpressing TIMP-1 showed 115% migration (P
AIM: To investigate the differential phosphorylation and activation of p38

in hepatocytes by pro-apoptotic Transforming Growth Factor-βi (TGF-β1), pro-survival factors Epidermal Growth Factor (EGF) and 12-0- tetradecanoylphorbol-13-acetate ABT-888临床试验 (TPA) and the potential mechanisms. METHODS: The phosphorylation and activation of p38 were determined by immunoblotting. Apoptosis was analyzed by morphological staining and observation, FACS analysis of

sub-G1 content and DNA fragmentation assay. To quantitatively determine caspase activation, caspase 激酶抑制剂分子库体外 activity assay was performed in vitro. RESULTS: TGF-β1-induced apoptosis was associated with the phosphorylation of p38, and SB202190, a specific inhibitor of p38, which was able to inhibit TGF-β1-induced caspase activation and apoptosis. TPA and EGF also blocked apoptosis induced by TGF-β1. Both of them induced the phosphorylation of p38. The results showed SB202190 had no effect on TGF-β1-induced phosphorylation of p38, but effectively inhibited both EGF and TPA-induced phosphorylation of p38. CONCLUSION: Pro-apoptotic TGF-β1, anti-apoptotic TPA and EGF induce the phosphorylation of p38 through different mechanisms that can be distinguished by SB202190. The data suggest that TPA and EGF-induced p38 phosphorylation is through an autophosphorylation-dependent mechanism. Since p38 phosphorylation induced by TGF-β1 plays an important role in caspase activation and apoptosis, TPA and EGF-induced p38 phosphorylation may not be requisite for their anti-apoptotic function.