Role of caspases in Ox-LDL-induced apoptotic cascade in XXXX coronary artery endothelial cells.

@entity1 @entity17205 @entity522 @entity588 @entity1182 @entity4674 @entity46964 @entity8186 @entity8187 @entity5353 @entity1839 @entity70959 @entity4493 @entity435
Oxidized low-density lipoprotein (ox-LDL) induces apoptosis in endothelial cells. However, steps leading to ox-LDL-induced apoptosis remain unclear. We examined the role of ox-LDL and its newly described receptor @entity4493 in the expression of intracellular pro- and antiapoptotic proteins and caspase pathways in @entity1 coronary artery endothelial cells (HCAECs). Cells were cultured and treated with different concentrations (10 to 80 microg/mL) of ox-LDL for different times (2 to 24 hours). Ox-LDL induced apoptosis in HCAECs in a concentration- and time-dependent manner. Ox-LDL also activated @entity8187 and @entity522 , but not @entity8186 . After ox-LDL treatment, there was a significant release of activators of @entity8187 , including @entity4674 and @entity17205 from mitochondria to cytoplasmic compartment, and their release was not affected by treatment of cells with inhibitors of either @entity8186 or @entity8187 . Ox-LDL also decreased expression of antiapoptotic proteins @entity588 and c-IAP (inhibitory apoptotic protein)-1, which are involved in the release of @entity4674 and @entity17205 and activation of @entity8187 , in a concentration- and time-dependent manner. On the other hand, ox-LDL did not change the expression of @entity1182 ( @entity1182 ) and proapoptotic protein Fas, which are required for the activation of @entity8186 . Further, ox-LDL did not cause the truncation of @entity5353 , which implies the activation of @entity8186 . In other experiments, pretreatment of HCAECs with the @entity8187 inhibitor @entity46964 , but not the @entity8186 inhibitor @entity70959 , blocked ox-LDL-induced activation of @entity522 and apoptosis. As expected, pretreatment with the @entity522 inhibitor DEVD- @entity435 inhibited ox-LDL-induced activation of @entity522 and resultant apoptosis. The proapoptotic effects of ox-LDL were mediated by its receptor @entity4493 , because pretreatment of HCAECs with antisense- @entity4493 , but not sense- @entity4493 , blocked these effects of ox-LDL. These findings suggest that ox-LDL through its receptor @entity4493 decreases the expression of antiapoptotic proteins @entity588 and @entity1839 . This is followed by activation of apoptotic signaling pathway, involving release of @entity4674 and @entity17205 and activation of @entity8187 and then @entity522 .
