Neuroprotective Role of a Proline-Rich Akt Substrate in Apoptotic Neuronal Cell Death after Stroke: Relationships with Nerve Growth Factor

• DOI: 10.1523/jneurosci.5209-03.2004
• Publication Date: 2004-02-18T20:02:48Z
• Authors: Atsushi Saito; Purnima Narasimhan; Takeshi Hayashi; Shuzo Okuno; Michel Ferrand-Drake; Pak H. Chan
• Keywords: Male; Neurons; 0303 health sciences; Caspase 3; Cell Survival; Blotting, Western; Gene Transfer Techniques; Apoptosis; Infarction, Middle Cerebral Artery; Disease Models, Animal; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Neuroprotective Agents; 14-3-3 Proteins; Gene Expression Regulation; Antibody Specificity; Caspases; Nerve Growth Factor; Animals; Enzyme Inhibitors; Adaptor Proteins, Signal Transducing

The Akt signaling pathway contributes to regulation of apoptosis after a variety cell death stimuli. A novel proline-rich substrate (PRAS) was recently detected and found be involved in apoptosis. In our study, activation modulated by growth factors, treatment with nerve factor (NGF) reduced apoptotic ischemic injury. However, the role PRAS neuronal ischemia remains unknown. Phosphorylated (pPRAS) binding pPRAS/phosphorylated (pPRAS/pAkt) 14-3-3 (pPRAS/14-3-3) were detected, their expression transiently decreased mouse brains transient focal cerebral (tFCI). Liposome-mediated pPRAS cDNA transfection induced overexpression pPRAS, promoted pPRAS/14-3-3, inhibited tFCI. pPRAS/pAkt, pPRAS/14-3-3 increased NGF-treated mice but inhibition phosphatidylinositol-3 kinase NGF receptor These results suggest that phosphorylation its interaction pAkt might play an important neuroprotection mediated