Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium

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Title Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium
Author Ashton, Kevin John; Nilsson, Ulrika; Willems, Laura; Holmgren, Kirsty; Headrick, John Patrick
Journal Name Biochemical and Biophysical Research Communications
Year Published 2003
Place of publication USA
Publisher Academic Press
Abstract The well-documented age-related change in ischemic tolerance may result from impaired adenosine-mediated cardioprotection. Additionally, ischemia itself may potentially modify adenosine signalling, contributing to the post-ischemic phenotype. This study investigates age- and ischemia-dependent changes in adenosine receptor transcript levels (Adora) for the A1, A2A, A2B, and A3 receptor subtypes in mouse myocardium. Hearts from young (2–4 months) and moderately aged (16–18 months) mice were subjected to 20-min ischemia and 45-min reperfusion. Ischemic tolerance was impaired in aged hearts, which recovered less than 30% ventricular pressure development (compared with ∼70% in young hearts), and lost 2-fold higher levels of lactate dehydrogenase during reperfusion (reflecting cellular disruption). Real-time PCR analyses revealed an age-related decline in Adora3 levels and induction of Adora2B. Curiously, this effect was mimicked by ischemia, which acutely reduced Adora3 levels and induced Adora2B in young (but not old) hearts. In contrast, in aged hearts ischemia selectively reduced levels of Adora1 transcript (∼2-fold) without altering transcript levels for the other receptors. These results demonstrate selective modulation of cardioprotective adenosine receptor transcription by both aging and ischemia. Reduced A3 adenosine receptor transcription may contribute to impaired ischemic tolerance in aged hearts, whereas changes in Adora transcription induced by ischemia may impact on the post-ischemic phenotype at later time points.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.bbrc.2003.10.127
Volume 312
Page from 367
Page to 372
ISSN 0006-291X
Date Accessioned 2004-04-07
Date Available 2015-05-04T01:49:07Z
Language en_US
Research Centre Griffith Health Institute; Heart Foundation Research Centre
Faculty Griffith Health Faculty
Subject PRE2009-Cardiology (incl. Cardiovascular Diseases)
URI http://hdl.handle.net/10072/6114
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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