Induction of endothelin-converting enzyme-1 in gastric mucosal injury by idomethacin.

Abstract:

:Endothelin-1 (ET-1) is a 21-amino acid vasoactive peptide produced from a 39-amino acid biologically inactive peptide, big ET-1, by the action of endothelin-converting enzyme-1 (ECE-1). We investigated gastric mucosal expression of ECE-1 during a 16 h course of inflammatory responses associated with gastric mucosal injury caused by indomethacin. The extent of gastric mucosal damage reached a maximum 4 h following the drug, and was accompanied by a 3.9-fold enhancement in the expression of ECE-1 activity and a significant elevation in ET-1 (4.5-fold), TNF-alpha (11.3-fold), and apoptosis (29.9-fold). A 37.2% decrease in the severity of lesion 16 h following the drug was associated with a 44.5% reduction in the mucosal expression of ECE-1 activity and a decline in TNF-alpha (64%), ET-1 (65.2%), and apoptosis (72.3%). The results demonstrate that gastric mucosal injury by indomethacin is associated with up-regulation of ECE-1 expression, which leads to the enhancement of ET-1 production, induction of TNF-alpha, and triggering apoptotic events that disrupt gastric mucosal homeostasis.

authors

Slomiany BL,Slomiany A

doi

10.1006/bbrc.2000.2299

subject

Has Abstract

pub_date

2000-03-16 00:00:00

pages

377-81

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)92299-X

journal_volume

269

pub_type

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