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apoptosis without the signs of cytochrome C release and activation of caspase 3 (von
Harsdorf et al. 1999). It is also found that both pathways of apoptosis caused an increase
in the expression of p53 protein, while the expression of Bax was found unchanged (von
Harsdorf et al. 1999). In contrast to this findings, a significant increase in the Bax
expression was reported in cells subjected to oxidative stress, which was produced by the
SOD inhibition (Siwik et al. 1999). Although the exact mechanisms of oxidative stress
induced-apoptosis in cardiac myocytes are still not known, the involvement of oxidative
stress and apoptosis in the pathogenesis of number of cardiovascular diseases is well
documented. Since these two factors coexist in same pathological situations, it is safe to
assume that they are interconnected.
IV. RETINOIC ACID
IY.a. Introduction and chemical structure
Retinoic acid, an active metabolite of retinol (vitamin A), is chemically defined as
3,7-Dimethyl-9-(2,6,6trimethy1-1-cyclohexen-1-YL)-2,4,6,8-nonatetraenoic
acid. The
conversion of retinol to retinoic acid is achieved bythe oxidation of by-products such as
retinal, through the action of number of enzymes including retinol and retinal
dehydrogenases. This conversion is also catabolyzed by several cytochrome P450s
enzymes (CYPs) such as CYP 141, CYP 142, C\? 1B1 and 344 (Chen et al. 2000b;
Duester 1996). Different isomeric forms of retinoic acid including all-trans retinoic acid,
13-cis retinoic acid and 9-cis retinoic acid are active regulators of the transcription of
number of genes (Fig. ). Other members of the group are 3,4 didehydro retinoic acid and
14-hydroxy-retro retinol, whose direct functions are still to be elucidated (Napoli 1996).
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