A specific inhibitor of p34cdc2/cyclin B suppresses fertilization-induced calcium oscillations in mouse eggs

被引:38
作者
Deng, MQ [1 ]
Sheldon, SS [1 ]
机构
[1] Iowa State Univ Sci & Technol, Dept Zool & Genet, Ames, IA 50011 USA
关键词
D O I
10.1095/biolreprod62.4.873
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Fertilization-induced Ca2+ oscillations in mouse eggs cease at the time of pronuclear formation when maturation-promoting factor (MPF) is inactivated, but the Ca2+ oscillations are ceaseless if eggs are arrested at metaphase by colcemid, which maintains the activity of MPF. To determine the possible role of MPF in regulation of cytoplasmic Ca2+ excitability, roscovitine, a specific inhibitor of p34(cdc2)/cyclin B kinase, was used to inactivate MPF, and its effect on fertilization-induced Ca2+ oscillations was investigated. Our results showed that roscovitine at greater than or equal to 50 mu M suppressed fertilization-induced Ca2+ oscillations in normal and colcemid-treated metaphase II (MII) eggs after the first 1-2 Ca2+ spikes. Roscovitine inhibition of fertilization-induced Ca2+ oscillations could be reversed by extensive washing of the eggs. Histone H1 kinase activity in colcemid-treated MII eggs was similarly inhibited by roscovitine, which suggested that the cessation of fertilization-induced Ca2+ oscillations is due to the inactivation of MPF. Thimerosal-induced Ca2+ oscillations in Ca2+-, Mg2+-free medium was also suppressed by roscovitine, suggesting a general inhibitory effect of roscovitine on Ca2+ oscillations. The inhibition may be achieved by disruption of Ca2+ release and refilling of the calcium store. Thapsigargin, an inhibitor of the endoplasmic reticulum Ca-ATPase, induced significantly less Ca2+ release in roscovitine-treated eggs than in the non-drug-treated eggs. Taken together, our results suggest that MPF plays an important role in regulation of the cytoplasmic Ca2+ excitability in mouse eggs.
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页码:873 / 878
页数:6
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