The Rai (Shc C) adaptor protein regulates the neuronal stress response and protects against cerebral ischemia

• DOI: 10.1073/pnas.0403283101
• Publication Date: 2004-10-20T01:19:17Z
• Authors: Flavia Troglio; Cinara Echart; Alberto Gobbi; Tony Pawson; Pier Giuseppe Pel...; Maria Grazia De S...; Giuliana Pelicci
• Keywords: Neurons; 0301 basic medicine; 0303 health sciences; Src Homology 2 Domain-Containing, Transforming Protein 3; Neuropeptides; 610; Protein Serine-Threonine Kinases; Brain Ischemia; Enzyme Activation; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Shc Signaling Adaptor Proteins; Proto-Oncogene Proteins; Animals; Phosphorylation; Proto-Oncogene Proteins c-akt

Rai (Shc C or N-Shc) is a neuron-specific member of the family Shc-like adaptor proteins. functions in cytoplasmic propagation Ret-dependent survival signals and regulates, vivo , number sympathetic neurons. We report here function Rai, i.e., regulation neuronal adaptive response to environmental stresses. demonstrate that ( i ) primary cultures cortical neurons from -/- mice are more sensitive apoptosis induced by hypoxia oxidative stress; ii mice, ischemia/reperfusion injury induces severe neurological deficits, increased size infarct area, significantly higher mortality; iii as stress-response gene increases phosphatidylinositol 3-kinase activation Akt phosphorylation after hypoxic oxidation insults. These data suggest has functional neuroprotective role brain injury, with possible implications treatment stroke.