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

Reichelt, Melissa E., Shanu, Anu, Willems, Laura, Witting, Paul K., Ellis, Natasha A., Blackburn, Michael R. and Headrick, John P. (2009) Endogenous adenosine selectively modulates oxidant stress via the A1 receptor in ischemic hearts. Antioxidants and Redox Signaling, 11 11: 2641-2650. doi:10.1089/ars.2009.2644


Author Reichelt, Melissa E.
Shanu, Anu
Willems, Laura
Witting, Paul K.
Ellis, Natasha A.
Blackburn, Michael R.
Headrick, John P.
Title Endogenous adenosine selectively modulates oxidant stress via the A1 receptor in ischemic hearts
Formatted title
Endogenous adenosine selectively modulates oxidant stress via the A1 receptor in ischemic hearts
Journal name Antioxidants and Redox Signaling   Check publisher's open access policy
ISSN 1523-0864
1557-7716
Publication date 2009-10
Sub-type Article (original research)
DOI 10.1089/ars.2009.2644
Open Access Status Not yet assessed
Volume 11
Issue 11
Start page 2641
End page 2650
Total pages 10
Place of publication New Rochelle, NY, United States
Publisher Mary Ann Liebert
Language eng
Formatted 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±0.7IU/g of lactate dehydrogenase (LDH). A1AR deletion worsened dysfunction and LDH efflux (15.2±2.6IU/g). Tissue cholesterol and native cholesteryl esters were unchanged, whereas cholesteryl ester-derived lipid hydroperoxides and hydroxides (CE-O(O)H; a marker of lipid oxidation) increased threefold, and α-tocopherylquinone [α-TQ; oxidation product of α-tocopherol (α-TOH)] increased sixfold. Elevations in α-TQ were augmented by two- to threefold 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: fourfold 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 that additional ARs (A2A, A2B, and/or A3) can mediate similar actions. These data reveal that local adenosine engages A1ARs during I/R to limit oxidant damage and enhance outcome selectively. Control of α-TOH/α-TQ levels may contribute to A1AR-dependent cardioprotection. 
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biomedical Sciences Publications
 
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