Effect of c-Jun NH₂-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.</p>

Effect of expression of c-jun N-terminal kinase on neuron autophagy following diffuse brain injury in rats / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effect and potential mechanism of expression of c-jun N-terminal kinase (JNK) signal pathway on neuron autophagy after diffuse brain injury (DBI).</p><p><b>METHODS</b>Male Sprague Dawley rats (n = 216) were randomly divided into four groups: DBI group (n = 54), SP600125 intervene group (n = 54), DMSO group (n = 54) and sham operation group (n = 54). DBI rat model was established according to the description of Marmarou DBI. At different time points (1, 6, 12, 24, 48 and 72 h) after operation, the histopathologic changes of neurons in cortex were observed by HE staining method; The expression of p-JNK, p-P53, DRAM and Beclin-1 were detected by Western blot and immunohistochemistry.</p><p><b>RESULTS</b>The results showed that under light microscope degenerated and necrotic neurons were observed to be scattered in cortex at 6 h after operation in DBI group, but these changes were low in SP600125 intervene group. Compared with SP600125 intervene group, the expression of p-JNK in DBI group were enhanced obviously at 6, 12 and 24 h (F = 17.902, P < 0.05); the expression of p-P53 in DBI group were enhanced obviously at 12, 24, 48 and 72 h (F = 7.107, P < 0.05); the expression of DRAM in DBI group were enhanced obviously at 6, 12, 24, 48 and 72 h (F = 15.455, P < 0.05); the expression of Beclin-1 in DBI group were enhanced obviously at 6, 12, 24, 48 and 72 h (F = 11.517, P < 0.05). Compared with DBI group, the expression of p-JNK, p-P53, DRAM and Beclin-1 in DMSO group were similar at 1, 6, 12, 24, 48 and 72 h (F = 1.509, P > 0.05).</p><p><b>CONCLUSIONS</b>The present results indicate that SP600125 can dramatically improve trauma brain injury from autophagy after DBI and the molecular mechanism is related to the modulation of JNK signal pathway following DBI, while it measures the neuron autophagy by means of intervening JNK signal pathway.</p>