Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium
Ashton, Kevin J., Nilsson, Ulrika, Willems, Laura, Holmgren, Kirsty, and Headrick, John P. (2003) Effects of aging and ischemia on adenosine receptor transcription in mouse myocardium. Biochemical and Biophysical Research Communications, 312 (2). pp. 367-372.
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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.
|Item Type:||Article (Refereed Research - C1)|
|Keywords:||aging; ischemia; adenosine receptors; gene expression; quantitative real-time PCR|
|Date Deposited:||16 Apr 2010 02:20|
|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%