il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
il\VOLVEMENT OF RETII\OIC ACID II{ - MSpace at the University of ...
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plays a significant role in <strong>the</strong> p<strong>at</strong>hogenesis <strong>of</strong> congestive heart failure (Og<strong>at</strong>a and<br />
Takahashi 2003; Yamauchi-Takihara and Kishimoto 2000). It is reported th<strong>at</strong> ET-l<br />
antiapoptotic effects on isol<strong>at</strong>ed cardiac myocytes were medi<strong>at</strong>ed through <strong>the</strong> activ<strong>at</strong>ion<br />
<strong>of</strong> c-Src tyrosine kinase, which results in <strong>the</strong> increased phosphoryl<strong>at</strong>ion <strong>of</strong> <strong>the</strong> STAT 3<br />
p<strong>at</strong>hway. Administr<strong>at</strong>ion <strong>of</strong> adriamycin to isol<strong>at</strong>ed neon<strong>at</strong>al cardiac myocytes caused an<br />
increase in <strong>the</strong> occurrence <strong>of</strong> apoptosis (Kunisada et al. 2002). The development <strong>of</strong><br />
apoptosis in this model was accompanied by <strong>the</strong> reduction <strong>of</strong> Bcl-xl expression<br />
(Kunisada et al. 2002). The over-expression <strong>of</strong> <strong>the</strong> Bcl-xl in <strong>the</strong> same model resulted in<br />
<strong>the</strong> decrease in <strong>the</strong> levels <strong>of</strong> apoptosis, however it failed to regul<strong>at</strong>e both adriamycininduced<br />
free radical production and cardiac-specific gene regul<strong>at</strong>ion (Kunisada et al.<br />
2002). Adenoviral vector-induced overexpression <strong>of</strong> Bcl-xl was also found to <strong>of</strong>fer a<br />
protection against <strong>the</strong> occurrence <strong>of</strong> apoptosis in <strong>the</strong> r<strong>at</strong> hearts subjected to ischemiareperfusion<br />
injury (Huang et al. 2003).<br />
Oxid<strong>at</strong>ive stress induced apoptosis was also found to be accompanied by a<br />
significant decrease in <strong>the</strong> Bcl-xl expression. The increase in apoptosis was also<br />
accompanied by a 3.2 fold increase in <strong>the</strong> Bcl-xslBcl-xl r<strong>at</strong>io (Galvez et al. 2001). The<br />
role <strong>of</strong> Bcl-xl in <strong>the</strong> prevention <strong>of</strong> apoptosis was also confirmed using <strong>the</strong> a number <strong>of</strong><br />
experimental models <strong>of</strong> heart failure. L<strong>at</strong>if et al (2000) (L<strong>at</strong>if et aI.2000) has reported an<br />
upregul<strong>at</strong>ion <strong>of</strong> Bcl-2 family proteins in <strong>the</strong> end stage heart failure. The concomitant<br />
increase in <strong>the</strong> Bcl-2 and Bcl-xl levels, accompanied by an increase in Bax expression<br />
was <strong>at</strong>tributed to <strong>the</strong> development <strong>of</strong> compens<strong>at</strong>ory antiapoptotic mechanisms in p<strong>at</strong>ents<br />
with heart failure. Ikeda et al. (2002) (Ikeda et aL 2002) has also reported an upregul<strong>at</strong>ion<br />
in both mRNA expression and protein levels <strong>of</strong> Bcl-xl in failing hearts<br />
a)