Akt phosphorylation and neuronal survival after traumatic brain injury in mice.
The serine-threonine kinase, Akt, is involved in the survival signaling pathways in many cell systems. The present study examined phosphorylation of Akt at serine-473 and DNA fragmentation after traumatic brain injury (TBI) in mice. Immunohistochemistry showed phospho-Akt was decreased in the injured cortex 1 h after TBI, whereas it was temporally increased at 4 h in the perifocal damaged cortex. In the CA1 region of the hippocampus, phospho-Akt was increased after TBI. Western blot analysis showed that Akt was significantly decreased as early as 1 h after trauma; however, the phosphorylation was accelerated at 4 h. Double staining with phospho-Akt and phospho-BAD or phospho-GSK-3beta revealed the colocalization of phospho-Akt and downstream elements. Double staining with phospho-Akt and terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling showed different cellular distributions after TBI. The present study implicates Akt phosphorylation in the signaling pathways that are involved in cell survival after TBI.
Noshita
Nobuo
N
Department of Neurosurgery, Program in Neurosciences, Stanford University School of Medicine, Stanford, California, USA.
Lewén
Anders
A
Sugawara
Taku
T
Chan
Pak H
PH
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation / Q000502:physiology; D018891:Dentate Gyrus / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D009474:Neurons / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000502:physiology
D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt