Gould M C, Stephano J L
Instituto de Biología Celular y Molecular, Ensenada, B.C, 22800, México.
Exp Cell Res. 2000 Oct 10;260(1):175-9. doi: 10.1006/excr.2000.5014.
In a previous study involving the inhibition of mitogen-activated protein kinase (MAPK) activation during fertilization of the marine worm Urechis caupo, we found that PD98059, but not U0126, caused multiple sperm penetrations in oocytes (Gould and Stephano, 1999, Dev. Biol. 216, 348-358). Since these oocytes are protected against polyspermy by a positive shift in membrane potential at fertilization (Gould-Somero et al., 1979, J. Cell Biol. 82, 426-440), we investigated the effects of PD98059 on the electrical properties of the oocyte membrane. PD98059, but not U0126, selectively blocked the voltage-dependent Ca(2+) channels that participate in the electrical polyspermy block. We also noted previously that PD98059 had more serious effects than U0126 on chromosome behavior during meiosis. This, too, could be explained by the effect on Ca(2+) channels, since when U0126-treated eggs were fertilized in low Ca(2+) seawater to reduce Ca(2+) uptake, similar effects were produced. These results show that PD98059 has side effects unrelated to the inhibition of MAPK activation and underscores the need for caution in interpreting the results of experiments with this widely used MEK inhibitor.
在之前一项关于抑制海蚯蚓Urechis caupo受精过程中有丝分裂原激活蛋白激酶（MAPK）激活的研究中，我们发现PD98059而非U0126会导致卵母细胞出现多个精子穿透现象（古尔德和斯特凡诺，1999年，《发育生物学》第216卷，第348 - 358页）。由于这些卵母细胞在受精时通过膜电位的正向变化来防止多精受精（古尔德 - 索梅罗等人，1979年，《细胞生物学杂志》第82卷，第426 - 440页），我们研究了PD98059对卵母细胞膜电特性的影响。PD98059而非U0126选择性地阻断了参与电多精受精阻断的电压依赖性Ca(2+)通道。我们之前还注意到，PD98059在减数分裂期间对染色体行为的影响比U0126更严重。这同样可以通过对Ca(2+)通道的影响来解释，因为当用U0126处理的卵在低Ca(2+)海水中受精以减少Ca(2+)摄取时，会产生类似的效果。这些结果表明，PD98059具有与抑制MAPK激活无关的副作用，并强调在解释使用这种广泛应用的MEK抑制剂的实验结果时需要谨慎。
