The University of Southampton
University of Southampton Institutional Repository

Urocortin protects cardiac myocytes from ischemia/reperfusion injury by attenuating calcium-insensitive phospholipase A2 gene expression

Lawrence, K.M., Scarabelli, T.M., Turtle, L., Chanalaris, A., Townsend, P.A., Carroll, C.J., Hubank, M., Stephanou, A., Knight, R.A. and Latchman, D.S. (2003) Urocortin protects cardiac myocytes from ischemia/reperfusion injury by attenuating calcium-insensitive phospholipase A2 gene expression The FASEB Journal, 17, (15), pp. 2313-2315. (doi:10.1096/fj.02-0832fje).

Record type: Article


We have used Affymetrix gene chip technology to look for changes in gene expression caused by a 24 h exposure of rat primary neonatal cardiac myocytes to the cardioprotective agent urocortin. We observed a 2.5-fold down-regulation at both the mRNA and protein levels of a specific calcium-insensitive phospholipase A2 enzyme. Levels of lysophosphatidylcholine, a toxic metabolite of phospholipase A2, were lowered by 30% in myocytes treated with urocortin for 24 h and by 50% with the irreversible iPLA2 inhibitor bromoenol lactone compared with controls. Both 4 h ischemia and ischemia followed by 24 h reperfusion caused a significant increase in lysophosphatidylcholine concentration compared with controls. When these myocytes were pretreated with urocortin, the ischemia-induced increase in lysophosphatidylcholine concentration was significantly lowered. Moreover, co-incubation of cardiac myocytes with urocortin, or the specific phospholipase A2 inhibitor bromoenol lactone, reduces the cytotoxicity produced by lysophosphatidylcholine or ischemia/reperfusion. Similarly, in the intact heart ex vivo we found that cardiac damage measured by infarct size was significantly increased when lysophoshatidylcholine was applied during ischemia, compared with ischemia alone, and that pre-treatment with both urocortin and bromoenol lactone reversed the increase in infarct size. This, to our knowledge, is the first study linking the cardioprotective effect of urocortin to a decrease in a specific enzyme protein and a subsequent decrease in the concentration of its cardiotoxic metabolite.

Full text not available from this repository.

More information

Published date: 16 October 2003
Keywords: child, biological, rna, pharmacology, pyrones, cell death, heart, kinetics, cardiac, antagonists & inhibitors, london, cultured, biology, molecular biology, messenger, protein, rats, enzymology, lysophosphatidylcholines, exposure, drug effects, cell survival, gene expression regulation, genetics, models, cells, injuries, enzyme inhibitors, gene expression, health, metabolism, phospholipases a, naphthalenes, myocardial reperfusion injury, cardiotonic agents, corticotropin-releasing hormone, myocytes, down-regulation, animals
Organisations: Human Genetics, Community Clinical Sciences, Infection Inflammation & Immunity, Medicine


Local EPrints ID: 59974
ISSN: 0892-6638
PURE UUID: af95fa5c-22bd-4bea-9501-48d7c5df3a3d

Catalogue record

Date deposited: 05 Sep 2008
Last modified: 17 Jul 2017 14:24

Export record


Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton:

ePrints Soton supports OAI 2.0 with a base URL of

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.