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 & Redox Signaling, 11 (11). pp. 2641-2650.

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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 approximately 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, whereas cholesteryl ester-derived lipid hydroperoxides and hydroxides (CE-O(O)H; a marker of lipid oxidation) increased threefold, and alpha-tocopherylquinone [alpha-TQ; oxidation product of alpha-tocopherol (alpha-TOH)] increased sixfold. Elevations in alpha-TQ were augmented by two- to threefold by A1AR deletion, whereas CE-O(O)H was unaltered. A(1)AR 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 microM 2-chloroadenosine; 2-CAD) countered effects of A1AR deletion on oxidant damage, HO-1, and tissue injury, indicating that additional ARs (A(2A), A(2B), 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 alpha-TOH/alpha-TQ levels may contribute to A1AR-dependent cardioprotection.

Item ID: 10017
Item Type: Article (Research - C1)
ISSN: 1557-7716
Date Deposited: 13 Apr 2010 01:55
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1199 Other Medical and Health Sciences > 119999 Medical and Health Sciences not elsewhere classified @ 50%
06 BIOLOGICAL SCIENCES > 0606 Physiology > 060699 Physiology not elsewhere classified @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920103 Cardiovascular System and Diseases @ 50%
97 EXPANDING KNOWLEDGE > 970102 Expanding Knowledge in the Physical Sciences @ 50%
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