Abstract 100: A Novel Anti-cell Death Mechanism by Targeting the Biosynthesis of Oligosaccharide in ER
The pathological expression of many of the deadly human diseases such as myocardial infarction, renal failure etc. is cell death. In cancer research, myriads of ways have been found to kill a cell. However, we are still craving for an applicable mechanism to prevent cell death. The majority of the current research is to directly target the apoptosis pathway. While some compounds have been developed, none of them are pharmaceutically important likely due to the inherent toxic nature of the target. Here, we report a novel mechanism to block the cell death pathway by activating the cells’ own protective programs coded for stress. Components of the unfolded protein response (UPS) in ER have been implicated in the protection of ischemia/reperfusion heart in recent research. By targeting the biosynthesis of oligosaccharide, which activated UPS as indicated by the expression of the ER chaperones Grp94 and Grp78, we were able to completely block the Hsp90 inhibitor induced apoptotic cell death as well as the oxidative stress (as exemplified by sodium nitroprusside, SNP) induced necrotic cell death in multiple cell lines. Caspase-3 activation and PARP cleavage were nearly completely inhibited. While awaiting further exploration, the biosynthesis of the oligosaccharide could turn out to be an applicable target for acute conditions such as cardiac injury because of its relatively safe nature.
Author Disclosures: X. Luo: None. W. Zhou: None. L. Wei: None. L. Wei: None. F. Zhang: None.
- © 2015 by American Heart Association, Inc.