Selective involvement of the PI3K/PKB/bad pathway in retinal cell death.
The phosphoinositide-3-kinase (PI3K)/protein kinase B (PKB)/Bad signal transduction pathway is engaged in the control of apoptosis in many different cell types, particularly through phosphorylation of the Bcl-2 family protein Bad. We examined the involvement of this pathway in the control of programmed cell death in the retina of developing rats. PKB is constitutively phosphorylated in retinal tissue in vitro, whereas Bad was dephosphorylated both in Ser112 and Ser136. Cell death induced by either the PI3K inhibitor LY294002, or the general kinase inhibitor 2-aminopurine, were followed by PKB dephosphorylation, but PKB was not modulated during cell death induced by the protein synthesis inhibitor anisomycin. Treatment of retinal tissue cultures with forskolin, which increases intracellular levels of cAMP, partially blocked apoptosis induced by both anisomycin and 2-aminopurine, but not by LY294002, whereas forskolin invariably induced phosphorylation of Bad on both Ser112 and Ser136. The data suggest that Bad may be engaged in survival pathways in the immature retina, but pathways other than PI3K/PKB/Bad, and phosphorylation sites other than Ser112 and Ser136 in the Bad protein control cell survival in retinal tissue.
Campos
Claudia B L
CB
Instituto de Biofísica da UFRJ, CCS, bloco G, Cidade Universitaria, Rio de Janeiro, RJ, Brasil 21949-900.
Bédard
Pierre-André
PA
Linden
Rafael
R
D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000502:physiology*; D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D019610:Cytoprotection / Q000502:physiology; D015151:Immunoblotting; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology* / Q000502:physiology*; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D051025:bcl-Associated Death Protein
D002352:Carrier Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012694:Serine; D051025:bcl-Associated Death Protein; C494821:Bad protein, rat