Document Detail


ADP-ribosylation factor 6 expression and activation are reduced in myometrium in complicated pregnancies.
MedLine Citation:
PMID:  22666423     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: ARF6 (ADP-ribosylation factor 6) small GTP binding protein plays critical roles in actin cytoskeleton rearrangements and membrane trafficking, including internalisation of G protein coupled receptors (GPCR). ARF6 operates by cycling between GDP-bound (inactive) and GTP-bound (active) forms and is a potential regulator of GPCR-mediated uterine activity during pregnancy and labour. ARF6 contains very low intrinsic GTP binding activity and depends on GEFs (guanine nucleotide exchange factors) such as CYTH3 (cytohesin 3) to bind GTP. ARF6 and CYTH3 were originally cloned from human placenta, but there is no information on their expression in other reproductive tissues.
METHODS: The expression of ARF6, ARF1, and CYTH1-4 was investigated by measuring mRNA (using RT-PCR) and protein levels (using immunoblotting) in samples of myometrium obtained from non-pregnant women, and women with normal pregnancies, before or after the spontaneous onset of labour. We also analysed myometrial samples from women with spontaneous preterm labour and from women with complicated pregnancies requiring emergency preterm delivery. The GST)-effector pull down assay was used to study the presence of active ARF6 and ARF1 in all myometrial extracts.
RESULTS: ARF6, ARF1 and CYTH3 but not CYTH1, CYTH2 and CYTH4 were expressed in all samples and the levels did not change with pregnancy or labour. However, ARF6 and CYTH3 but not ARF1 levels were significantly reduced in complicated pregnancies. The alterations in the expression of ARF6 and its GEF in human myometrium indicate a potential involvement of this signalling system in modulating the response of myometrial smooth muscle in complicated pregnancies. The levels of ARF6-GTP or ARF1-GTP did not change with pregnancy or labour but ARF6-GTP levels were significantly decreased in women with severe complications of pregnancy.
CONCLUSIONS: We have demonstrated a functional ARF6 system in human myometrium and a correlation between ARF6 level and activity in uterine and abnormal pregnancy.
Authors:
Venkateswarlu Kanamarlapudi; Sian E Owens; Jon Lartey; Andrés López Bernal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-30
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-06-05     Completed Date:  2012-10-29     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e37954     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ADP-Ribosylation Factor 1 / genetics,  metabolism
ADP-Ribosylation Factors / genetics*,  metabolism*
Cell Line, Tumor
Enzyme Activation
Female
Gene Expression Regulation, Enzymologic*
Guanine Nucleotide Exchange Factors / genetics,  metabolism
Guanosine Triphosphate / metabolism
Humans
Myometrium / enzymology,  metabolism*,  pathology
Placenta / metabolism,  pathology
Pregnancy
Pregnancy Complications / enzymology*,  genetics,  pathology
RNA, Messenger / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
G0401232//Medical Research Council
Chemical
Reg. No./Substance:
0/Guanine Nucleotide Exchange Factors; 0/RNA, Messenger; 86-01-1/Guanosine Triphosphate; EC 3.6.5.2/ADP-Ribosylation Factor 1; EC 3.6.5.2/ADP-Ribosylation Factors; EC 3.6.5.2/ADP-ribosylation factor 6
Comments/Corrections

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