Imperial College London
Alternate

ProfessorMarkJohnson

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Chair in Obstetrics
 
 
 
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Contact

 

+44 (0)20 3315 7887mark.johnson

 
 
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Location

 

H3.35Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Chen:2012:10.1111/j.1582-4934.2011.01413.x,
author = {Chen, L and Sooranna, SR and Lei, K and Kandola, M and Bennett, PR and Liang, Z and Grammatopoulos, D and Johnson, MR},
doi = {10.1111/j.1582-4934.2011.01413.x},
journal = {Journal of Cellular and Molecular Medicine},
pages = {1447--1460},
title = {Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells},
url = {http://dx.doi.org/10.1111/j.1582-4934.2011.01413.x},
volume = {16},
year = {2012}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Cyclic AMP (cAMP) is the archetypal smooth muscle relaxant, mediating the effects of many hormones and drugs. However, recently PGI2, acting via cAMP/PKA, was found to increase contractionassociated protein expression in myometrial cells and to promote oxytocindriven myometrial contractility. Cyclooxygenase2 (COX2) is the ratelimiting enzyme in prostaglandin synthesis, which is critical to the onset and progression of human labour. We have investigated the impact of cAMP on myometrial COX2 expression, synthesis and activity. Three cAMP agonists (8bromocAMP, forskolin and rolipram) increased COX2 mRNA expression and further studies confirmed that this was associated with COX2 protein synthesis and activity (increased PGE2 and PGI2 in culture supernatant) in primary cultures of human myometrial cells. These effects were neither reproduced by specific agonists nor inhibited by specific inhibitors of known cAMPeffectors (PKA, EPAC and AMPK). We then used shRNA to knockdown the same effectors and another recently described cAMPeffector PDZGEF12, without changing the response to cAMP. We found that MAPK activation mediated the cAMP effects on COX2 expression and that PGE2 acts through EP2 to activate MAPK and increase COX2. These data provide further evidence in support of a dual role for cAMP in the regulation of myometrial function.
AU  - Chen,L
AU  - Sooranna,SR
AU  - Lei,K
AU  - Kandola,M
AU  - Bennett,PR
AU  - Liang,Z
AU  - Grammatopoulos,D
AU  - Johnson,MR
DO  - 10.1111/j.1582-4934.2011.01413.x
EP  - 1460
PY  - 2012///
SN  - 1582-4934
SP  - 1447
TI  - Cyclic AMP increases COX-2 expression via mitogen-activated kinase in human myometrial cells
T2  - Journal of Cellular and Molecular Medicine
UR  - http://dx.doi.org/10.1111/j.1582-4934.2011.01413.x
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000305791600010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://onlinelibrary.wiley.com/doi/full/10.1111/j.1582-4934.2011.01413.x
UR  - http://hdl.handle.net/10044/1/72534
VL  - 16
ER  -
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