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Effect of c-Jun NH₂-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats.
Chin Med J (Engl) 2012; 125(11):2019-24CM

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.

CONCLUSION

JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.

Authors+Show Affiliations

Department of Surgery, Hebei Medical University, Shijiazhuang, Hebei 050017, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22884071

Citation

Hong, Ming-Yan, et al. "Effect of c-Jun NH₂-terminal Kinase-mediated P53 Expression On Neuron Autophagy Following Traumatic Brain Injury in Rats." Chinese Medical Journal, vol. 125, no. 11, 2012, pp. 2019-24.
Hong MY, Gao JL, Cui JZ, et al. Effect of c-Jun NH₂-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats. Chin Med J. 2012;125(11):2019-24.
Hong, M. Y., Gao, J. L., Cui, J. Z., Wang, K. J., Tian, Y. X., Li, R., ... Wang, H. (2012). Effect of c-Jun NH₂-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats. Chinese Medical Journal, 125(11), pp. 2019-24.
Hong MY, et al. Effect of c-Jun NH₂-terminal Kinase-mediated P53 Expression On Neuron Autophagy Following Traumatic Brain Injury in Rats. Chin Med J. 2012;125(11):2019-24. PubMed PMID: 22884071.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of c-Jun NH₂-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats. AU - Hong,Ming-Yan, AU - Gao,Jun-Ling, AU - Cui,Jian-Zhong, AU - Wang,Kai-Jie, AU - Tian,Yan-Xia, AU - Li,Ran, AU - Wang,Hai-Tao, AU - Wang,Huan, PY - 2012/8/14/entrez PY - 2012/8/14/pubmed PY - 2013/1/12/medline SP - 2019 EP - 24 JF - Chinese medical journal JO - Chin. Med. J. VL - 125 IS - 11 N2 - 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. CONCLUSION: JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI. SN - 2542-5641 UR - https://www.unboundmedicine.com/medline/citation/22884071/Effect_of_c_Jun_NH₂_terminal_kinase_mediated_p53_expression_on_neuron_autophagy_following_traumatic_brain_injury_in_rats_ L2 - http://Insights.ovid.com/pubmed?pmid=22884071 DB - PRIME DP - Unbound Medicine ER -