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

et al. lggg). The studies using a same model have also reported that ATRA
administration caused an inhibition of the H2}2-tnggered activation of c-fLIN N-
terminal kinase (JNK) pathway which resulted in the protection of mesanglial cells
against HzOz-induced apoptosis (Moreno-Manzano et al' 1999)
Retinoic acid also has proven its apoptosis regulatory characteristics when used in
combination with antineoplastic drugs. Retinoic acid, in combination with the
anthracycline antineoplastic drug-daunorubicin, was found to cause apoptosis in the non-
M3 AML, the cells that are usually resistant to chemotherapy (Lehmann et al. 2000).
However, the effects of RA on apoptosis with and without adriamycin have not been
examined. The regulation of apoptosis by retinoic acid is achieved by two separate
p athways : receptor-dep endant and rec eptor indep endent p athway.
IV.e.l.Receptor-dependent pathway: The study performed by Konta et al' (200i) has
shown that a pretreatment with RAR (AGN 193109) or RXR ( HX53i) pan-agonists or a
transient transfection with dominant-negative RAR and RXR mutants results in the
attenuation of anti-apoptotic effects of all-trans retinoic acid (ATRA) on HzOz-treated
mesanglial cells (Konta et al. 2001). The use of both RAR and RXR antagonists was
found to reverse suppressive effects of ATRA on the Ap-l activity. However, the
separate effect of RAR or RXR antagonists on the suppression of Ap-l was found to be
different. The RAR antagonist are found to abolish ATRA's suppressive effects on both
c-jun and c-fos, while RXR antagonists resulted in the reversal of ATRA's suppressive
effects on the c-fos but not the c-jun (Konta et al' 2001).
However, usage of both RAR and RXR antagonists as well as dominant negative RA and
RXR mutants did not effect the ATRA's suppression of JNK activity. This indicates the
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