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

adriamycin induced heart failure. However, the direct link between the oxidative stress,
apoptosis and development of adriamycin-induced heart failure still remains to be
established.
Retinol, vitamin A, is found to be involved in the regulation of processes essential
for life such as growth, development, differentiation and proliferation. One of the main
mechanisms involved in the control of growth is apoptosis. Retinoic acid, a metabolite of
retinol, binds to two super-families of intranuclear receptors (RAR and RXR). Each of
these families consist of three specific isoforms (o,F,y).The activation of these receptors
results in the expression of number of genes including the ones important in apoptosis.
The complexity of retinoic acid signaling is charactenzed by the fact that both RAR and
RXR receptors dimenze in order to exhibit their effects. RAR receptors require
obligatory heterodymerization with RXR whereas the RXR receptors homodimerize with
themselves and/or heterodimerize with other intranuclear receptors such as peroxisome
proliferation activator receptors (PPAR's). PPAR receptors are also shown to be
involved in the regulation of apoptosis. Depending on the cell type, concentration and
dimerization, retinoic acid is known to have a dual effect i.e. it can cause or prevent
apoptosis. Although the role of retinoic acid in the regulation of apoptosis in some cell
types is well established, its role in the regulation of apoptosis in adult cardiac myocytes
remains to be examined.
Since adriamycin-induced oxidative stress can cause apoptosis and since retinoic
acid may be involved in the regulation of apoptosis, we hypothesized that oxidative stress
induced changes in retinoic acid receptors may play a role in adriamycin-induced