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Ethanol preconditioning is dependent on the activation of 5′‐AMP‐activated protein kinase
Author(s) -
Gaskin Frederick Spencer,
Kamada Kazuhiro,
Yusof Mozow,
Rubin Leona J.,
Korthuis Ronald J.
Publication year - 2007
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.21.6.a1220-c
Subject(s) - ampk , enos , protein kinase a , chemistry , ischemia , amp activated protein kinase , nitric oxide , nitric oxide synthase , phosphorylation , medicine , endocrinology , pharmacology , biochemistry
We have previously demonstrated that consuming ethanol at low levels 24 hr prior to ischemia/reperfusion (EPC) prevents postischemic leukocyte‐endothelial cell adhesive interactions (LEI) by a mechanism that is initiated by nitric oxide (NO) formed by endothelial NO synthase (eNOS). Recent work indicates that: ethanol increases the activity of 5′‐AMP‐activated protein kinase (AMPK) and AMPK phosphorylates eNOS at Ser1177. In light of these observations, we postulated that AMPK may play a role in triggering the development of the anti‐inflammatory phenotype induced by EPC. Ethanol was administered to C57BL/6 mice by gavage in the presence or absence of AMPK inhibition. 24 hrs later, the numbers of rolling and adherent leukocytes in the small intestine were recorded using an intravital microscopic approach after 45 min of ischemia and 60 min of reperfusion (I/R) or at equivalent time points in control animals. I/R induced a marked increase in LEI relative to sham control mice. The increase in LEI was prevented by EPC, an effect that was lost with AMPK inhibition during the period of ethanol exposure. Pilot data in AMPK α2 KO mice suggests that the anti‐inflammatory effect of EPC is dependent on this isoform. Our results indicate that the beneficial actions of ethanol ingestion to prevent postischemic leukocyte rolling and adhesion are initiated by an AMPK‐dependent mechanism. Supported by AA14945 and DK 43785.