il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
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In this study we analyzed <strong>the</strong> d<strong>at</strong>a for combined RAR and RXR receptor levels as<br />
well as vari<strong>at</strong>ions in <strong>the</strong> RAR/RXR receptor r<strong>at</strong>io in response to different interventions.<br />
ADR group animals exhibited a significant increase in <strong>the</strong> RAR/RXR receptor r<strong>at</strong>io due<br />
to a higher increase in <strong>the</strong> RAR receptor levels <strong>the</strong>n RXR receptors. The increase in RAR<br />
receptors and RAR/R)G- receptor r<strong>at</strong>io may indic<strong>at</strong>e an increased potential for retinoic<br />
acid signaling, due to <strong>the</strong> factth<strong>at</strong>RAR receptors are oblig<strong>at</strong>e heterodimeric partners with<br />
RXR receptors. In our in vitro studies <strong>the</strong> tre<strong>at</strong>ment with low doses <strong>of</strong> adriamycin to<br />
ADR group myocytes resulted in an increased expression <strong>of</strong> RAR receptors. In vitro<br />
adriamycin tre<strong>at</strong>ment did not cause any significant change in <strong>the</strong> total RXR receptor<br />
levels but resulted in a significant increase in RAR/RXR r<strong>at</strong>io. These findings correl<strong>at</strong>e<br />
with our in vivo studies.<br />
Although it is known th<strong>at</strong> adriamycin administr<strong>at</strong>ion causes apoptosis (Kumar et<br />
al. 1999; Kumar et al. 2001), present study shows for <strong>the</strong> first time th<strong>at</strong> adriamycin also<br />
causes an increase in <strong>the</strong> RAR/RXR receptor r<strong>at</strong>io in ADR group hearts. This can be<br />
seen to promote heterodimeriz<strong>at</strong>ion and such an adriamycin-induced disruption <strong>of</strong><br />
retinoic acid signaling process may lead to <strong>the</strong> occurrence <strong>of</strong> apoptosis and may be a<br />
caus<strong>at</strong>ive factor in <strong>the</strong> adriamycin-induced heart failure. The administr<strong>at</strong>ion <strong>of</strong> probucol<br />
to adriamycin tre<strong>at</strong>ed animals decreased <strong>the</strong> RAR/RXR receptor r<strong>at</strong>io, this was mainly<br />
due to a rel<strong>at</strong>ively higher increase in <strong>the</strong> RXR receptor levels. This change in r<strong>at</strong>io can be<br />
seen to increase homodimenz<strong>at</strong>ionas well as retinoic acid signaling which can lead to <strong>the</strong><br />
protection against adriamycin-induced apoptosis. In vitro studies also showed th<strong>at</strong> <strong>the</strong><br />
antioxidant trolox resulted in a decrease in <strong>the</strong> RARIRXR r<strong>at</strong>io in <strong>the</strong> ADR+TROL group<br />
myocytes. Trolox has been shown to modul<strong>at</strong>e adriamycin-induced apoptosis in this<br />
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