title: Effect of c-Jun NH₂-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats.
abstract: BACKGROUND
  Activation of c-Jun NH(2)-terminal kinase (JNK) has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury (TBI). However, the underlying molecular pathway remains unclear. Our study assessed whether JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.
  
  
  METHODS
  A total of 186 male Sprague-Dawley (SD) rats (300 - 350 g) were used in this study. By randomized block method rats were randomly divided into four groups: sham-operated (n = 46), TBI (n = 60), TBI + dimethyl sulfoxide (DMSO) (n = 40), and TBI + SP600125 (n = 40). JNK was treated with SP600125, a specific JNK inhibitor. JNK, p-P53, Beclin-1, damage-regulated autophagy modulator (DRAM) and p-bcl-2 were evaluated by Western blotting analysis. The cellular localization and expression of Beclin-1 and DRAM was observed by immunofluorescence and immunohistochemistry, and the expression of Beclin-1-Bcl-2/Bcl-xL complexes was evaluated by immunoprecipitation. Multiple-group comparisons were conducted using analysis of variance (ANOVA). P values of less than 0.05 were considered statistically significant.
  
  
  RESULTS
  It was observed that the expression of JNK, p-P53, Beclin-1, DRAM and p-bcl-2 was increasing after TBI, and the expression of Beclin-1 and DRAM was mainly located in the cytoplasm of neurons. But these were significantly inhibited in SP600125 group compared with sham group and TBI + SP600125 group (P < 0.05). The expression of Beclin-1-Bcl-2/Bcl-xL complexes was reduced after TBI.
  
  
  CONCLUSIONS
  JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.
authors.affiliation: Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, China.
authors.forename: Ming-Yan
authors.initials: MY
authors.lastname: Hong
authors.forename: Jun-Ling
authors.initials: JL
authors.lastname: Gao
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Cui
authors.forename: Kai-Jie
authors.initials: KJ
authors.lastname: Wang
authors.forename: Yan-Xia
authors.initials: YX
authors.lastname: Tian
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Wang
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D000071186:Beclin-1; D015153:Blotting, Western; D001930:Brain Injuries / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494813:Bcl2l1 protein, rat; D000071186:Beclin-1; C512829:Becn1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051020:bcl-X Protein; D048031:JNK Mitogen-Activated Protein Kinases