PMID:14973226

Citation	Saito, A, Narasimhan, P, Hayashi, T, Okuno, S, Ferrand-Drake, M and Chan, PH (2004) Neuroprotective role of a proline-rich Akt substrate in apoptotic neuronal cell death after stroke: relationships with nerve growth factor. J. Neurosci. 24:1584-93
Abstract	The Akt signaling pathway contributes to regulation of apoptosis after a variety of cell death stimuli. A novel proline-rich Akt substrate (PRAS) was recently detected and found to be involved in apoptosis. In our study, Akt activation was modulated by growth factors, and treatment with nerve growth factor (NGF) reduced apoptotic cell death after ischemic injury. However, the role of the PRAS pathway in apoptotic neuronal cell death after ischemia remains unknown. Phosphorylated PRAS (pPRAS) and the binding of pPRAS/phosphorylated Akt (pPRAS/pAkt) to 14-3-3 (pPRAS/14-3-3) were detected, and their expression transiently decreased in mouse brains after transient focal cerebral ischemia (tFCI). Liposome-mediated pPRAS cDNA transfection induced overexpression of pPRAS, promoted pPRAS/14-3-3, and inhibited apoptotic neuronal cell death after tFCI. The expression of pPRAS, pPRAS/pAkt, and pPRAS/14-3-3 increased in NGF-treated mice but decreased with inhibition of phosphatidylinositol-3 kinase and the NGF receptor after tFCI. These results suggest that PRAS phosphorylation and its interaction with pAkt and 14-3-3 might play an important role in neuroprotection mediated by NGF in apoptotic neuronal cell death after tFCI.
Links	PubMed Online version:10.1523/JNEUROSCI.5209-03.2004
Keywords	14-3-3 Proteins; Adaptor Proteins, Signal Transducing; Animals; Antibody Specificity; Apoptosis/drug effects; Apoptosis/physiology; Blotting, Western; Caspase 3; Caspases/metabolism; Cell Survival/drug effects; Cell Survival/physiology; Disease Models, Animal; Enzyme Inhibitors/pharmacology; Gene Expression Regulation; Gene Transfer Techniques; Infarction, Middle Cerebral Artery/physiopathology; Male; Mice; Nerve Growth Factor/metabolism; Nerve Growth Factor/pharmacology; Neurons/drug effects; Neurons/metabolism; Neuroprotective Agents/pharmacology; Phosphatidylinositol 3-Kinases/antagonists & inhibitors; Phosphatidylinositol 3-Kinases/metabolism; Phosphoproteins/genetics; Phosphoproteins/metabolism; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-akt; Signal Transduction/drug effects; Signal Transduction/physiology; Stroke/physiopathology; Tyrosine 3-Monooxygenase/metabolism
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