Peer-Reviewed Journal Details
Mandatory Fields
Gomez-Vicente, V,Doonan, F,Donovan, M,Cotter, TG;
2006
June
The European Journal of Neuroscience
Induction of BIMEL following growth factor withdrawal is a key event in caspase-dependent apoptosis of 661W photoreceptor cells
Validated
()
Optional Fields
cones development mouse phosphoinositide 3-kinase serum starvation BCL-2 FAMILY-MEMBERS FORKHEAD TRANSCRIPTION FACTOR RETINAL DEVELOPMENT BH3-ONLY PROTEINS MITOCHONDRIAL INTEGRITY NEURONAL APOPTOSIS SIGNALING PATHWAY RELATIVE BIM NITRIC-OXIDE BH3 DOMAINS
24
981
990
Apoptosis of photoreceptor cells in the early postnatal period is a normal feature of mammalian retinal development. The role of mitochondria and caspases in the process has been well established; however, the identification of key apoptotic mediators still remains elusive. Here we report that BIMEL, a pro-apoptotic BCL-2 family member, may be one such molecule. Following growth factor deprivation, BIMEL was up-regulated in mouse 661W cone photoreceptors. This event correlated with the release of mitochondrial apoptogenic factors into the cytosol, the activation of caspases and apoptosis. Moreover, a similar behaviour was observed in response to UV radiation, ionomycin or H2O2 treatments. We identified the PI3K-Akt-FKHRL1 signalling cascade as the main regulatory pathway of BIMEL expression in these cells. Finally, using RNA interference, we were able to silence BIMEL expression and subsequently suppress caspase-3 activation. In conclusion, we propose BIMEL as a critical factor in mitochondria-dependent apoptosis of 661W photoreceptors.
DOI 10.1111/j.1460-9568.2006.04990.x
Grant Details