il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...

examined all these individual receptors with multitude of interventions including
different concentrations of adriamycin (4,8 and 10 pM), different concentrations of
retinoic acid (0.1 and lpM), lipid soluble antioxidant (probucol) and water soluble
antioxidant (trolox). These data revealed multiple of specific changes in the listed
isoforms of retinoic acid receptors. Because of different directionalities of there changes,
it is difficult to make a simple conclusion. However, PROB group data provide an
indication that changes in the RA receptors can be brought about not only through the
modification of gene expression but also through direct membrane as well as lipid
changes due to these interventions. Thus further detailed studies are required for each of
the isoforms to fully understand the significance of different isoforms.
It is important to state that a study of the ratio of total RAR and total RXR, as is
done here, provides avery clear cut message that an increase in this ratio correlates with
an increase in Bax/Bcl-xl ratio and such an increase is promoted by an increase in
oxidative stress. Based on the data obtained in my study as well as on the information
available in literature, it is established that adriamycin induces oxidative stress. The latter
influences the expression of RAR and RXR receptors such that the ratio of RAR/RXR is
increased. This increase in receptor ratio modifies both proapoptotic and antiapoptotic
proteins, Bax and Bcl-xl respectively to cause an increase in apoptosis. Interference in
this proposed chain of events (Fig. 33) with appropriate antioxidant therapy in this study
is shown to reduce apoptosis.
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