Document Detail

Fertilization stimulates long-lasting oscillations of CaMKII activity in mouse eggs.
MedLine Citation:
PMID:  15242787     Owner:  NLM     Status:  MEDLINE    
Elucidation of the biochemical mechanisms by which specific proteins transduce the all important intracellular calcium (Ca2+) signal at fertilization into events of egg activation will increase our understanding of the regulation of the onset of development and the extent to which these signals can be experimentally modified. Previously, we reported data supporting the hypothesis that mouse eggs have the capability to generate oscillations of the activity of Ca2+ and calmodulin-dependent kinase II (CaMKII), regulating the cell cycle and secretion. This study directly demonstrates transient increases of enzyme activity in relatively close synchrony with Ca2+ oscillations for the first hour of fertilization in single mouse eggs monitored for both Ca2+ and CaMKII activity. The extent of the enzyme activity increase was correlated with the level of intracellular Ca2+. After a rise in activity, the decrease in activity did not appear to be due to negative feedback from elevated Ca2+ or CaMKII activity over time, since enzyme activity persisted after 8 min of elevated Ca2+ from 7% ethanol activation. The contribution of CaMKII from a single sperm to the rise in CaMKII activity at fertilization appeared to be negligible. Also, long-term cell cycle inhibition was observed in fertilized eggs with the CaMKII antagonist myrAIP (50 microM), which did not inhibit the first large Ca2+ transient or subsequent early oscillations but did reduce the percentage of eggs fertilized. Thus, mammalian eggs appear to drive many activation events over time to completion with repeated short bursts of Ca2+ oscillation-dependent CaMKII activity, rather than by a steady-state, continuously elevated level of CaMKII activity that is maintained by periodic Ca2+ oscillations.
Styliani Markoulaki; Sara Matson; Tom Ducibella
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Developmental biology     Volume:  272     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-09     Completed Date:  2004-09-17     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  15-25     Citation Subset:  IM    
Sackler School of Biomedical Sciences, Program in Cell, Molecular and Developmental Biology, Tufts University School of Medicine, Boston, MA 02111, USA.
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MeSH Terms
Calcium / metabolism
Calcium Signaling
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors,  metabolism*
Cells, Cultured
Cycloheximide / pharmacology
Enzyme Activation
Enzyme Inhibitors / pharmacology
Fertilization / physiology*
Mice, Inbred Strains
Oocytes / drug effects,  metabolism
Peptides / pharmacology
Signal Transduction
Sperm Capacitation / physiology
Sperm-Ovum Interactions
Spermatozoa / enzymology
Time Factors
Zygote / metabolism*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Peptides; 0/myristoylated autocamtide-2-related inhibitory peptide; 66-81-9/Cycloheximide; 7440-70-2/Calcium; EC Protein Kinase Type 2; EC Protein Kinases

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