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

presence of two distinctive pathways of ATRA's antiapoptotic activity; the nuclear
receptor dependent and the nuclear receptor independent pathway. A study done by
Szondy et al. (1998) explored the role of retinoic acid receptors in the inhibition of
activation-induced apoptosis in thymocytes (Szondy et al. 1998b). This study
documented that inhibitory effects of ATRA on the activation-induced apoptosis in
thymocytes were mediated through the activation of RAR o receptors. This was
confirmed by the fact that ATRA effects were inhibited by the addition of RAR cr
antagonists (Szondy et al. 1998b). The same study has reported that stimulation by RAR
y resulted in the enhancement of activation-induced apoptosis of thymocytes and
abolished the effects of RAR a activation (Szondy et al. 1998b). This study concluded
that in normal physiological situations there is a balance between the RAR cr antiapoptotic
and RAR y pro-apoptotic effects. However, the occulrence of 9-cis RA will
cause the activation of RXR receptors, which may tip the balance toward the
heterodymeization with RAR cr and prevention of apoptosis (Szondy et al. i998a). This
indicates that 9-cis retinoic acid may be a critical element in the regulation of apoptosis in
positive selection of th¡rmocytes. The induction of apoptosis, caused by the activation of
RAR y receptor, is mediated by the activation of apoptosis-inducing endonucleases and
tissue transglutaminases (Szony Z and Reichert U et al. 1998). The role of retinoic acid
receptors in the regulation of apoptosis is also confirmed by the study of Toma et al.
(1998) (Toma et al. 1998). This study has shown that both ATRA and 13-cis RA are able
to induce apoptosis in the MCF-7 breast carcinoma cell line (Toma s, Isnardi L et al.
1993). This was achieved by the activation of RAR cr, RAR y and RXR o (Toma et al.
19e8).
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