Abstract
PURPOSE: HB-EGF is synthesized as a membrane-anchored form (proHB-EGF) and proHB-EGF is cleaved on the cell surface to yield soluble HB-EGF by the mechanism called "ectodomain shedding". The aim of this study is to determine whether various stress induce ectodomain shedding of proHB-EGF. MATERIALS AND METHODS: Vero-H cells were cultured for 15h in serum free MEM-NEAA, then treated with anisomycin, sorbitol, or H2O2. For UV and X-ray irradiation, Vero-H were exposed to 40 mJ UV using a Spectrolinker and 1 Gy using X-ray generator, respectively. Following incubation for 30 min with stimili, the cells were collected and shedding was detected by western blot analysis. RESULT: An inhibitor of p38 MAPK inhibited the stress-induced ectodomain shedding of proHB-EGF. The stress induced shedding was inhibited neither by the inhibitor of TPA- or LPA- induced shedding , nor by dn forms of molecules involved in TPA- or LPA- induced proHB-EGF shedding pathway. [J Radiat Res 44:423 (2003)]