X-Radiation-Induced Down-Regulation of the EGF Receptor in Primary Cultured Rat Hepatocytes
X-Radiation-Induced Down-Regulation of the EGF Receptor in Primary Cultured Rat Hepatocytes
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DOI：
10.1667/rr1793.1
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发表时间：
2010-05-01
影响因子：
3.4
通讯作者：
Ohkubo, Yasuhito
中科院分区：
文献类型：
--
作者：
Maruko, Akiko;Ohtake, Yosuke;Ohkubo, Yasuhito
暴露在X射线辐射下与肝脏的增殖活性下降有关，但其分子机制(S)尚不清楚。我们利用门静脉周围肝细胞(PPH)和静脉周围肝细胞(PVH)，研究了X射线照射是否参与了表皮生长因子(EGF)受体(EGFR)的功能变化，从而导致EGF诱导的DNA合成减少，这两种细胞的增殖活性不同。X射线辐射剂量依赖性地降低了两个亚群的DNA合成。PPH组DNA合成的下降速度大于PVH组，但经10GyX射线照射后，这种带状差异消失。[I-125]EGF结合研究表明，X射线照射后，两个亚群的高亲和力EGFR表达下调。此外，X射线照射后两个亚群中EGF诱导的EGFR二聚化和Y1173位的磷酸化均下调，且PPH的下调幅度大于PVH。相反，在两个亚群中，EGF治疗后Y845位的磷酸化在X射线照射后呈剂量依赖性上调。这些结果表明，辐射引起的EGF诱导的DNA合成下降至少部分是由EGFR功能改变引起的。(C)2010年，由辐射研究学会提供
Exposure to X radiation is associated with a decline in the proliferative activity of the liver, but the molecular mechanism(s) is not well understood. We investigated whether exposure to X radiation is involved in functional changes in the epidermal growth factor (EGF) receptor (EGFR), thereby causing a reduction of EGF-induced DNA synthesis using periportal hepatocytes (PPH) and perivenous hepatocytes (PVH), which differ in their proliferative activity. X radiation dose-dependently decreased DNA synthesis in both subpopulations. The rate of decline in the DNA synthesis was greater in PPH than in PVH, but the zonal difference disappeared after exposure to 10 Gy X radiation. [I-125]EGF binding studies indicated that high-affinity EGFRs in both subpopulations were down-regulated after X irradiation. Furthermore, EGF-induced EGFR dimerization and phosphorylation at Y1173 in both subpopulations were down-regulated after X irradiation, and the rate of decline was greater in PPH than in PVH. In contrast, phosphorylation at Y845 after EGF treatment was dose-dependently up-regulated after X irradiation in both subpopulations. These results suggest that the X-radiation-related decline in EGF-induced DNA synthesis is caused at least partly by the modification of EGFR function. (C) 2010 by Radiation Research Society