Document Detail


Elevated levels of uterine anti-apoptotic signaling may activate NFKB and potentially confer resistance to caspase 3-mediated apoptotic cell death during pregnancy in mice.
MedLine Citation:
PMID:  21566000     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Preserving the uterus in a state of relative quiescence is vital to the maintenance of a successful pregnancy. Elevated cytoplasmic levels of uterine caspase 3 during pregnancy have been proposed as a potential regulator of uterine quiescence through direct targeting and disabling of the uterine contractile architecture. However, despite highly elevated levels of uterine caspase 3 during pregnancy, there is minimal evidence of apoptosis. This current study defines the mechanism whereby the pregnant uterine myocyte may harness the tocolytic activity of active caspases while avoiding apoptotic cell death. Using the pregnant mouse model, we have analyzed the uterus for changes in pro- and antiapoptotic signaling patterns associated with the advancing stages of pregnancy. Briefly, we have found that members of the IAP family, such as SURVIVIN and XIAP, and the Bcl2 family members, such as MCL1, are elevated in the uterine myocyte during late gestation. The IAP family members are the only endogenous inhibitors of active caspase 3, and MCL1 limits activation of caspase 3 by suppressing proapoptotic signaling. Elevated XIAP levels partner with SURVIVIN, resulting in increased levels of the antiapoptotic MCL1 via NFKB activation; these together have the potential to limit both the activity and level of active caspase 3 in the pregnant uterus as term approaches. We propose that modification of these antiapoptotic signaling partners allows the pregnant uterus to escape the apoptotic action of elevated active caspase 3 levels but also functions to limit the levels of active uterine caspase 3 near term.
Authors:
Pancharatnam Jeyasuria; Kalpana Subedi; Arvind Suresh; Jennifer C Condon
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-12
Journal Detail:
Title:  Biology of reproduction     Volume:  85     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-25     Completed Date:  2012-07-31     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  417-24     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / physiology*
Caspase 3 / genetics,  metabolism*
DNA / metabolism
Female
Genome
Mice
NF-kappa B / genetics,  metabolism*
Poly(ADP-ribose) Polymerases / genetics,  metabolism
Pregnancy
Uterus / cytology,  physiology*
Grant Support
ID/Acronym/Agency:
1R01HD065011-01A1/HD/NICHD NIH HHS; R01 HD065011/HD/NICHD NIH HHS; R01 HD065011-02/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/NF-kappa B; 9007-49-2/DNA; EC 2.4.2.30/Parp1 protein, mouse; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/Caspase 3
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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