Endogenous adenosine selectively modulates oxidant stress via the A1 receptor in ischemic hearts

There are no files associated with this record.

Title Endogenous adenosine selectively modulates oxidant stress via the A1 receptor in ischemic hearts
Author Reichelt, Melissa Elizabeth; Shanu, Ana; Willems, Laura; Witting, Paul K.; Ellis, Natasha A.; Blackburn, Michael R.; Headrick, John Patrick
Journal Name Antioxidants & Redox Signaling
Year Published 2009
Place of publication United States
Publisher Mary Ann Liebert, Inc.
Abstract We tested the impact of A1 adenosine receptor (AR) deletion on injury and oxidant damage in mouse hearts subjected to 25 min ischemia/45 min reperfusion (I/R). Wild-type hearts recovered ~50% of contractile function, and released 8.2±0.7 IU/g of lactate dehydrogenase (LDH). A1AR deletion worsened dysfunction and LDH efflux (15.2±2.6 IU/g). Tissue cholesterol and native cholesteryl esters were unchanged, while cholesteryl ester-derived lipid hydroperoxides and hydroxides (CE-O(O)H; a marker of lipid oxidation) increased 3-fold, and α-tocopherylquinone (α-TQ; oxidation product of α-tocopherol (α-TOH)) increased 6-fold. Elevations in α-TQ were augmented 2- to 3-fold by A1AR deletion, whereas CE-O(O)H was unaltered. A1AR deletion also decreased glutathione redox status ([GSH]/[GSSG+GSH]) and enhanced expression of the antioxidant response element heme oxygenase-1 (HO-1) during I/R: 4-fold elevations in HO-1 mRNA and activity were doubled by A1AR deletion. Broad-spectrum AR agonism (10 µM 2-chloroadenosine; 2-CAD) countered effects of A1AR deletion on oxidant damage, HO-1, and tissue injury, indicating additional ARs (A2A, A2B and/or A3) can mediate similar actions. These data reveal local adenosine engages A1ARs during I/R to selectively limit oxidant damage and enhance outcome. Control of α-TOH/α-TQ levels may contribute to A1AR-dependent cardioprotection.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1089/ars.2009.2644
Copyright Statement Copyright 2009 Mary Ann Liebert, Inc., publishers. Self-archiving of the author-manuscript version is not yet supported by this publisher. Please refer to the journal link for access to the definitive, published version or contact the authors for more information.
Volume 11
Issue Number 11
Page from 2641
Page to 2650
ISSN 1523-0864
Date Accessioned 2009-06-25
Date Available 2010-06-16T05:42:15Z
Language en_AU
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject Animal Physiology - Cell; Biochemistry and Cell Biology; Cardiology (incl Cardiovascular Diseases)
URI http://hdl.handle.net/10072/29430
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

Brief Record

Griffith University copyright notice