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Oocyte activation and passage through the metaphase/anaphase transition of the meiotic cell cycle is blocked in clams by inhibitors of HMG-CoA reductase activity.
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MedLine Citation:
PMID:  7896878     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cell cycle progression for postembryonic cells requires the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R), the enzyme which catalyzes the production of the isoprenoid precursor, mevalonate. In this study, we examine the requirements of HMG-R activity for cell cycle progression during the meiotic and early mitotic divisions using oocytes and dividing embryos from the surf clam, Spisula solidissima. Using two different inhibitors of HMG-R, we find that the activity of this enzyme appears to be required at three distinct points of the cell cycle during meiosis. Depending on the stage at which these inhibitors are added to synchronous clam cultures, a reversible cell cycle block is triggered at the time of activation or at metaphase of either meiosis I or II, whereas there is not block to the mitotic cell cycle. Inhibition of HMG-R activity in activated oocytes does not affect the transient activation of p42MAPK but results in a block at metaphase of meiosis I that is accompanied by the stabilization of cyclins A and B and p34cdc2 kinase activity. Our results suggest that metabolites from the mevalonate biosynthetic pathway can act to influence the process of activation, as well as the events later in the cell cycle that lead to cyclin proteolysis and the exit from M phase during clam meiosis.
Authors:
J E Turner; C G Minkoff; K H Martin; R Misra; K I Swenson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of cell biology     Volume:  128     ISSN:  0021-9525     ISO Abbreviation:  J. Cell Biol.     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-04-24     Completed Date:  1995-04-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0375356     Medline TA:  J Cell Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1145-62     Citation Subset:  IM    
Affiliation:
Department of Molecular Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bivalvia / cytology*
Cell Cycle / drug effects
Cyclins / metabolism
Female
Hydroxymethylglutaryl CoA Reductases / metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors*
Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent
Lovastatin / pharmacology
Meiosis / drug effects
Microtubules / drug effects,  metabolism
Oocytes / cytology*
Chemical
Reg. No./Substance:
0/Cyclins; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 75330-75-5/Lovastatin; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases; EC 1.1.1.34/Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): J Cell Biol
ISSN: 0021-9525
ISSN: 1540-8140
Publisher: The Rockefeller University Press
Article Information
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Print publication date: Day: 2 Month: 3 Year: 1995
Volume: 128 Issue: 6
First Page: 1145 Last Page: 1162
ID: 2120409
Publisher Id: 95204534
PubMed Id: 7896878

Oocyte activation and passage through the metaphase/anaphase transition of the meiotic cell cycle is blocked in clams by inhibitors of HMG-CoA reductase activity


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