In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 101, No. 43 ( 2004-10-26), p. 15476-15481
Abstract:
Rai (Shc C or N-Shc) is a neuron-specific member of the family of Shc-like adaptor proteins. Rai functions in the cytoplasmic propagation of Ret-dependent survival signals and regulates, in vivo , the number of sympathetic neurons. We report here a function of Rai, i.e., the regulation of the neuronal adaptive response to environmental stresses. We demonstrate that ( i ) primary cultures of cortical neurons from Rai -/- mice are more sensitive to apoptosis induced by hypoxia or oxidative stress; ( ii ) in Rai -/- mice, ischemia/reperfusion injury induces severe neurological deficits, increased apoptosis and size of the infarct area, and significantly higher mortality; and ( iii ) Rai functions as a stress-response gene that increases phosphatidylinositol 3-kinase activation and Akt phosphorylation after hypoxic or oxidation insults. These data suggest that Rai has a functional neuroprotective role in brain injury, with possible implications in the treatment of stroke.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.0403283101
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2004
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12