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Abstract #23436 Published in IGR 11-2
Effect of γ-synuclein silencing on apoptotic pathways in retinal ganglion cells
Surgucheva I; Shestopalov VI; Surguchov AJournal of Biological Chemistry 2008; 283: 36377-36385
γ-Synuclein (Syn G) is highly expressed in retinal ganglion cells and the loss of these cells in glaucoma is associated with significant reduction of the intracellular Syn G level. However, a causative relationship between these two events has not been established. Here we show that the knockdown of Syn G results in a decreased viability of the immortalized retinal ganglion cells (RGC-5). The Syn G silencing reduces phosphorylation of serine 112 (Ser (112)) in Bad protein, a member of the Bcl-2 family that plays a critical role in apoptotic cell death signaling. Our gene expression analysis data suggests that changes in Bad phosphorylation status may be caused by a coordinated shift in activities of kinases controlling Bad phosphorylation and phosphatases catalyzing its dephosphorylation. Moreover, increased phosphorylation of Bad-sequestering protein 14-3-3 detected in these cells is also pro-apoptotic. These results suggest that the homeostatic level of Syn G in RGC-5 cells is required for transcriptional regulation of protein kinases and phosphatases, controlling phosphorylation of Bad and 14-3-3. Lowering Syn G causes Bad dephosphorylation, dissociation from phosphorylated 14-3-3, and translocation to mitochondria where it initiates apoptotic death cascade.
A. Surguchov. Laboratory of Retinal Biology, Veterans Administration Medical Center, KS City, MO, 4801 Linwood Blvd., KS City, MO 64128, United States. asurguchov@kumc.edu
Classification:
3.6 Cellular biology (Part of: 3 Laboratory methods)
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
