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such as; increased generation of reactive oxygen species (ROS), phosphorylation of p53,
upregulation of proapoptotic protein Bax and its translocation to mitochondria, release of
cytochrome C and activation of caspase 9 and 3 (Simbula et al. 2004). Some of the new
studies indicate the potential usage of PPAR 1in
the treatment of antineoplastic disorders
such as multþ|e myeloma and human myeloid leukemia (Eucker et aL.2004; Liu et al.
2005). The usage of PPAR 7 synthetic (piogltazone, rosiglitazone) and natural ligands
(15-deoxy-Â12'la prostangladin J2) was shown to cause an apoptosis, in a dose dependent
manner.
A number of studies have confirmed both pro and antiapoptotic nature of retinoic
acid. Shaw et al. (2003) has reported that retinoic acid does not activate PPAR o and
PPAR y, however, it exhibits a high affinity for the activation of PPAR p/ô. The
activation of both retinoic acid receptor and PPAR B/ô will result in the initiation of
proapoptotic signaling cascade resulting in cellular death (Shaw et al.2003).PPARs are
shown to play a significant role in the regulation of apoptosis in a number of different cell
types, however, the role of PPARs in the apoptosis in the heart remains to be explored.
The abundance of PPAR B/ô in heart and its role as proapoptotic factor in other tissues
makes it an ideal target for the future exploration of the role of PPAR receptors in the
pathogenesis of heart failure.
V.d. PPAR and oxidative stress
The exact role of PPAR receptors in the pathogenesis of oxidative stress is still
being elicited, Since PPAR receptors are involved in the regulation of the process of
inflammation and since inflammation is one of the main processes which can cause the
increased production of free radicals indicate that PPAR may play a significant role in the
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