کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4352974 | 1298168 | 2009 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Preconditioning neuroprotection in global cerebral ischemia involves NMDA receptor-mediated ERK-JNK3 crosstalk
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کلمات کلیدی
CREBJnkNMDAN-methyl-d-aspartatec-Jun-N-terminal kinaseterminal deoxynucleotidyl transferase biotin-dUTP nick end labelingERK1/2 - ERK1 / 2MAPK - MAPKGlobal cerebral ischemia - ایسکمی مغز جهانیTUNEL - تونلCell signaling - سیگنالینگ سلولیHippocampus - هیپوکامپ cyclic adenosine monophosphate response element binding protein - پروتئین اتصال دهنده عنصر پاسخ آدنوزین مونوفسفره چرخهextracellular signal-regulated kinase 1/2 - کیناز 1/2 تنظیم سیگنال خارج سلولیmitogen-activated protein kinases - کیناز پروتئین فعال Mitogen
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Previous work has demonstrated that ischemic preconditioning neuroprotection is associated with inhibition of JNK pathway activation. The present study was designed to examine the hypothesis that the suppression of JNK3 activation by preconditioning is mediated by NMDA receptors and crosstalk between ERK1/2 and JNK3. Preconditioning (3Â min ischemia) 2 days before global cerebral ischemia (8-min) markedly decreased neuronal degeneration in hippocampus CA1, an effect abolished by pretreatment with the NMDA receptor antagonist, MK-801. Furthermore, preconditioning abolished cerebral ischemia-induced JNK3 activation and enhanced ERK1/2 activation, an effect reversed by MK-801. Due to the inverse relationship between ERK1/2 and JNK3 activation following preconditioning, we hypothesized that ERK1/2 may regulate JNK3 activation following preconditioning. In support of this contention, pretreatment with the MEK inhibitor, PD98059 significantly attenuated preconditioning-induced ERK1/2 phosphorylation, and strongly reversed preconditioning down-regulation of JNK3 phosphorylation. This finding suggests that ERK1/2 signaling is responsible for preconditioning-induced down-regulation of JNK3 activation. Western blot analysis and immunohistochemistry further demonstrated that preconditioning, in an NMDA-dependent manner, enhanced activation of the pro-survival factors, p-CREB and Bcl-2, while attenuating activation of putative pro-death factors, p-c-Jun and Fas-L in the hippocampus CA1. As a whole, the study demonstrates that preconditioning attenuation of pro-death JNK3 in the hippocampus CA1 following global cerebral ischemia is mediated by NMDA receptor-induced crosstalk between ERK1/2 and JNK3. The ERK1/2-mediated reduction of JNK3 activation leads to enhanced pro-survival signaling (P-CREB and Bcl-2 induction) and attenuation of pro-death signaling (p-c-Jun and Fas-L), with subsequent induction of ischemic tolerance.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Research - Volume 63, Issue 3, March 2009, Pages 205-212
Journal: Neuroscience Research - Volume 63, Issue 3, March 2009, Pages 205-212
نویسندگان
Quan-Guang Zhang, Rui-Min Wang, Dong Han, Li-Cai Yang, Jie Li, Darrell W. Brann,