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

plays a significant role in the pathogenesis of congestive heart failure (Ogata and
Takahashi 2003; Yamauchi-Takihara and Kishimoto 2000). It is reported that ET-l
antiapoptotic effects on isolated cardiac myocytes were mediated through the activation
of c-Src tyrosine kinase, which results in the increased phosphorylation of the STAT 3
pathway. Administration of adriamycin to isolated neonatal cardiac myocytes caused an
increase in the occurrence of apoptosis (Kunisada et al. 2002). The development of
apoptosis in this model was accompanied by the reduction of Bcl-xl expression
(Kunisada et al. 2002). The over-expression of the Bcl-xl in the same model resulted in
the decrease in the levels of apoptosis, however it failed to regulate both adriamycininduced
free radical production and cardiac-specific gene regulation (Kunisada et al.
2002). Adenoviral vector-induced overexpression of Bcl-xl was also found to offer a
protection against the occurrence of apoptosis in the rat hearts subjected to ischemiareperfusion
injury (Huang et al. 2003).
Oxidative stress induced apoptosis was also found to be accompanied by a
significant decrease in the Bcl-xl expression. The increase in apoptosis was also
accompanied by a 3.2 fold increase in the Bcl-xslBcl-xl ratio (Galvez et al. 2001). The
role of Bcl-xl in the prevention of apoptosis was also confirmed using the a number of
experimental models of heart failure. Latif et al (2000) (Latif et aI.2000) has reported an
upregulation of Bcl-2 family proteins in the end stage heart failure. The concomitant
increase in the Bcl-2 and Bcl-xl levels, accompanied by an increase in Bax expression
was attributed to the development of compensatory antiapoptotic mechanisms in patents
with heart failure. Ikeda et al. (2002) (Ikeda et aL 2002) has also reported an upregulation
in both mRNA expression and protein levels of Bcl-xl in failing hearts
a)