Appearance of shortened Bcl-2 and Bax proteins and lack of evidence for apoptosis in rat forebrain after severe experimental traumatic brain injury.
To investigate whether apoptosis plays a role in traumatic brain injury (TBI), we examined the expression of Bcl-2 and Bax proteins and the release of mitochondrial cytochrome c in rat brains using Western blot analysis. Bcl-2 at the predicted 26 kDa was not detected in controls and TBI groups. However, at 1 h post-TBI, a shortened Bcl-2 protein with a molecular size of approximately 14.5 kDa was detected in the injured hemisphere (R). At 4 and 12 h post TBI, an additional bcl-2 band ( approximately 10 kDa) was detected in R. Both bands disappeared at 14 days post-injury. The predicted 21-kDa band of Bax was detected in both controls and TBI animals. In addition, two shortened Bax proteins ( approximately 18 kDa) were detected after TBI. The time course of appearance was similar to that of Bcl-2 described above. In the present study, neither cytochrome c release from mitochondria nor DNA fragmentation was detected in the forebrains of sham and TBI groups. Treatment of animals with an antioxidant N-acetylcysteine administered ip greatly diminished the levels of shortened Bcl-2 and Bax proteins. These findings suggest that the induction of shortened Bcl-2 and Bax proteins in rat brains may be associated with reactive oxygen species generated after TBI.
Xiong
Y
Y
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. yexiong@med.wayne.edu
Lin
H
H
Chen
B D
BD
Peterson
P L
PL
Lee
C P
CP
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001930:Brain Injuries / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003574:Cytochrome c Group / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D016548:Prosencephalon; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494828:Bax protein, rat; D003574:Cytochrome c Group; D016166:Free Radical Scavengers; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D000111:Acetylcysteine