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Early intestinal tight junction loss after hemorrhagic shock
Author(s) -
Thuijls Geertje,
Haan JaccoJuri,
Derikx Joep P,
Bamburg Jim R,
Heineman Erik,
Buurman Wim A
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1120.15
Subject(s) - tight junction , cytoskeleton , actin , claudin , actin cytoskeleton , cofilin , microbiology and biotechnology , occludin , chemistry , biology , cell , biochemistry
The intestinal barrier is based on tight junctions (TJ) between intact epithelial cells. These TJ are anchored via the filamentous (F‐)actin cytoskeleton. We hypothesize that hemorrhagic shock (HS) leading to intestinal hypoperfusion, causes loss of F‐actin, via activation of Actin Depolymerizing Factor/Cofilin (AC), and consequently results in TJ loss. This study investigates intestinal AC activation and cytoskeleton severing following HS. Rats were subjected to HS and sacrificed, along with controls, at 15, 30, 60 and 90 min after induction of shock. Intestinal hypoperfusion, activation of AC, actin cytoskeleton severing (degradation of F‐ into globular actin), and TJ integrity loss (Claudin‐3, ZO‐1) were assessed. HS caused intestinal hypoperfusion (−71.7% bloodflow) and activation of AC from 15 min after HS (by 21%, P<0.05 vs controls, student's t‐test (stt)). This was accompanied by actin cytoskeleton severing, followed by intestinal TJ loss from 30 min after HS (Claudin‐3: 100% vs 71%; ZO‐1: 100% vs 41%, p<0.05 vs controls, stt). We show for the first time that HS results rapidly in intestinal hypoperfusion, AC activation, actin depolymerization and subsequent TJ loss. Elucidation of the etiology of barrier failure is a first step in understanding the disease entity, which will be followed by the development of therapeutic interventions to reduce the development of barrier failure.