RGD Reference Report - Endothelin-converting enzyme-1-mediated signaling in adult rat ventricular myocyte contractility and apoptosis during sepsis. - Rat Genome Database

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Endothelin-converting enzyme-1-mediated signaling in adult rat ventricular myocyte contractility and apoptosis during sepsis.

Authors: Gupta, A  Aberle NS, 2ND  Ren, J  Sharma, AC 
Citation: Gupta A, etal., J Mol Cell Cardiol. 2005 Mar;38(3):527-37.
RGD ID: 1581735
Pubmed: PMID:15733912   (View Abstract at PubMed)
DOI: DOI:10.1016/j.yjmcc.2005.01.002   (Journal Full-text)

We hypothesized that modulation of endothelin-converting enzyme-1 (ECE-1) activity would affect phosphorylation of p38-mitogen activated protein kinase (p38-MAPK) and potentiate apoptosis in adult rat ventricular myocytes (ARVMs) during sepsis. The activity of ECE-1 in ARVMs was altered by increasing the substrate availability for ECE-1 by exogenous administration of bigendothelin-1 (bigET-1, 100 nM) and by inhibiting ECE-1 using FR901533 (10 microM) for 24-h. FR901533 significantly decreased the concentration of ET-1 in both sham and sepsis groups. FR901533 decreased p38-MAPK phosphorylation in sepsis but not in sham group. BigET-1 upregulated p38-MAPK phosphorylation, produced hypertrophy, decreased cell viability and reversed FR901533-induced down-regulation of p38-MAPK phosphorylation in both groups. Although, FR901533 did not affect cell cross-sectional area, it significantly reduced the viability of ARVM in both groups. The peak shortening of sham ARVMs was elevated by bigET-1, FR901533 and pretreatment with FR901533 followed by bigET-1. However, the contractility of septic ARVMs was not altered by either bigET-1 or FR901533 treatments per se. Septic ARVM exhibited significantly increased caspase-3 activity at 12 and 24-h. Pretreatment with FR901533 significantly elevated caspase-3 activity in both sham and sepsis group. The data demonstrated that bigET-1-induced hypertrophy in septic ARVM correlates with an ECE-1 dependent-activation of p38-MAPK. The results suggest that non-responsiveness of ARVM to bigET-1 is due to ECE-1 dependent apoptosis. We concluded that ECE-1 may play a crucial role in ARVM dysfunction via increased caspase-3 activity and p38-MAPK phosphorylation during sepsis.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of G protein-coupled receptor signaling pathway  IMP 1581735 RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
endothelin signaling pathway  ISOEce1 (Rattus norvegicus)1581735; 1581735 RGD 
endothelin signaling pathway  IMP 1581735 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Ece1  (endothelin converting enzyme 1)

Genes (Mus musculus)
Ece1  (endothelin converting enzyme 1)

Genes (Homo sapiens)
ECE1  (endothelin converting enzyme 1)


Additional Information