CRH-like peptides protect cardiac myocytes from lethal ischaemic injury

Simulated ischaemia causes both necrotic and apoptotic death of primary cultures of neonatal rat cardiac myocytes. Simulated ischaemia is associated with increased expression of urocortin mRNA and with the release of urocortin peptide into the medium. Exogenous urocortin is more potent than corticot...

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Published in:	Molecular and cellular endocrinology Vol. 158; no. 1; pp. 55 - 63
Main Authors:	Brar, Bhawanjit K, Stephanou, Anastasis, Okosi, Anne, Lawrence, Kevin M, Knight, Richard A, Marber, Michael S, Latchman, David S
Format:	Journal Article
Language:	English
Published:	Ireland Elsevier Ireland Ltd 20-12-1999
Subjects:	Animals Animals, Newborn Apoptosis Cell Death Cells, Cultured Corticotropin releasing hormone Corticotropin-Releasing Hormone - antagonists & inhibitors Corticotropin-Releasing Hormone - metabolism Flow Cytometry In Situ Nick-End Labeling Myocardial ischaemia Myocardial Ischemia - metabolism Myocardium - metabolism Myocardium - pathology Rats Rats, Sprague-Dawley Reverse Transcriptase Polymerase Chain Reaction Transcription factors Urocortin Urocortins Corticotropin releasing hormone Myocardial ischaemia Urocortin Transcription factors Apoptosis
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Summary:	Simulated ischaemia causes both necrotic and apoptotic death of primary cultures of neonatal rat cardiac myocytes. Simulated ischaemia is associated with increased expression of urocortin mRNA and with the release of urocortin peptide into the medium. Exogenous urocortin is more potent than corticotropin releasing hormone (CRH) in protecting cardiac myocytes from necrotic and apoptotic death induced by ischaemia, and the cardioprotective effects of ischaemia-preconditioned media are abrogated by antagonists to the CRH family of peptides. Simulated ischaemia increases cardiac myocyte expression of CCAAT enhancer binding (C/EBP) transcription factors, and of the p65 subunit of NFκB, and reporter activity of a construct incorporating a fragment of the urocortin promoter containing a C/EBP consensus site is also enhanced by simulated ischaemia. The data suggest that ischaemia, acting partly through increased expression of C/EBP transactivators, increases expression of urocortin mRNA, which is rapidly translated to the mature form. The mature peptide is rapidly released, and exerts autocrine/paracrine protective effects through the cardiac CRH-R2 receptor which preferentially binds urocortin.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0303-7207 1872-8057
DOI:	10.1016/S0303-7207(99)00183-5