Inducers of JNK/SAPK and p38 kinase do not activate the same hypoxia-responsive elements that stimulate VEGF promoter activity in Ha-ras transformed cells (NIH3T3R). (A) Effect of JNK/SAPK and p38 kinase activators on the induction of a 385-bp VEGF reporter construct in NIH3T3R cells. NIH3T3R cells were left untreated or treated with 0.02% oxygen (HYP), TNF-α (200 U/mL), epidermal growth factor (EGF, 30 ng/mL), anisomycin (Anis, 30 ng/mL), sodium chloride (NaCl, 0.1 mol/L), or sorbitol (0.2 mol/L) for 7 hours before luciferase measurement. UV light was applied at 40 J/m2 24 hours before luciferase measurement. The relative fold induction refers to the ratio of luciferase activity measured in treated cells relative to the activity observed in the untreated controls. Values represent the means of at least three independent experimental results. Error bars represent 1 SD of the mean. (B) Comparison of JNK/SAPK activity induced by anisomycin with JNK/SAPK activity induced by 0.02% oxygen (HYP 0, 30, and 60 minutes) and 3.9% oxygen or 0.02% oxygen with or without reoxygenation after 0 minutes or 30 minutes. Values represent at least three independent experiments.
