FIG. 7.

Treatment of PAE cells with ROS enhances expression of ADAM9 and shedding of EphB4. (A) The level of expression of ADAM9 in immortalized PAE cells was increased by treatment with 250 or 500 μM H₂O₂. Expression of ADAM9 was detected by Western blotting with antibodies against the cytoplasmic domain of human ADAM9. (B to D) Increasing concentrations of H₂O₂ (10 to 500 μM) enhanced the shedding of transfected EphB4 from PAE cells (B) but had no effect on the shedding of the ADAM10 substrate BTC (C) or the ADAM17 substrate TNF-α (D). Since EphB4 can be cleaved by overexpressed ADAM9, whereas BTC and TNF-α are not (10, 28), these results suggest that H₂O₂ stimulates ADAM9-dependent shedding of EphB4 in PAE cells.