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PRAS40 plays a pivotal role in protecting against stroke by linking the Akt and mTOR pathways.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2014 Jun; Vol. 66, pp. 43-52. Date of Electronic Publication: 2014 Feb 27. - Publication Year :
- 2014
-
Abstract
- The proline-rich Akt substrate of 40kDa (PRAS40) protein is not only a substrate of the protein kinase Akt but also a component of the mTOR complex 1 (mTORC1), thus it links the Akt and the mTOR pathways. We investigated the potential protective role of PRAS40 in cerebral ischemia and its underlying mechanisms by using rats with lentiviral over-expression of PRAS40 and mice with PRAS40 gene knockout (PRAS40 KO). Our results show that gene transfer of PRAS40 reduced infarction size in rats by promoting phosphorylation of Akt, FKHR (FOXO1), PRAS40, and mTOR. In contrast, PRAS40 KO increased infarction size. Although the PRAS40 KO under normal condition did not alter baseline levels of phosphorylated proteins in the Akt and mTOR pathways, PRAS40 KO that underwent stroke exhibited reduced protein levels of p-S6K and p-S6 in the mTOR pathway but not p-Akt, or p-PTEN in the Akt pathway. Furthermore, co-immunoprecipitation suggests that there were less interactive effects between Akt and mTOR in the PRAS40 KO. In conclusion, PRAS40 appears to reduce brain injury by converting cell signaling from Akt to mTOR.<br /> (Copyright © 2014. Published by Elsevier Inc.)
- Subjects :
- Adaptor Proteins, Signal Transducing genetics
Animals
Brain pathology
Brain physiopathology
Brain Ischemia pathology
Brain Ischemia physiopathology
Cell Death
Cells, Cultured
Forkhead Box Protein O1
Forkhead Transcription Factors metabolism
Gene Transfer Techniques
Mice, Inbred C57BL
Mice, Knockout
Nerve Tissue Proteins metabolism
Neurons physiology
Phosphoproteins genetics
Phosphorylation
Rats, Sprague-Dawley
Signal Transduction
Stroke pathology
Adaptor Proteins, Signal Transducing metabolism
Phosphoproteins metabolism
Proto-Oncogene Proteins c-akt metabolism
Stroke physiopathology
TOR Serine-Threonine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 66
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 24583056
- Full Text :
- https://doi.org/10.1016/j.nbd.2014.02.006