E-ISSN 2636-865X
Research Article
C-Jun N-Terminal Kinase Mediates Calcitonin Gene-Related Peptide Expression in Rat Trigeminal Ganglion in Vitro
1 Department of Neurology, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, PR China  
2 Faculty of biochemical and molecular biology department, School of Medicine, Xi’an Jiaotong University, Xi’an  
3 Department of Pharmacology, School of Medicine, Xi’an Jiaotong University, Xi’an 710061, Shaanxi Province, PR China  
4 Division of Ear, Nose and Throat Diseases, CLINTEC, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden  
Neurol Sci Neurophysiol 2012; 29: 566-575

Key Words: CGRP; migraine; sumatriptan; JNK; cytokines
Abstract

Objective: Calcitonin gene-related peptide (CGRP) plays a prominent role in migraine pathophysiology. However, the underlying molecular mechanisms that are responsible for regulating CGRP expression are not fully understood. Using an in-vitro model of organ culture of rat trigeminal ganglion (TG), the present study aims to investigate the role of c-Jun N-terminal kinase (JNK) in regulation of CGRP.

Methods: The TG was isolated from Sprague-Dawley (SD) rats and then organ cultured in presence of inflammatory cytokines tumor necrosis factor-alpha (TNF-α) (50μg/L) or interleukin-1β (IL-1β) (25μg/L) with and without a specific JNK inhibitor SP600125 (10-5M) or an anti-migraine drug sumatriptan (0.5g/L) for 24h. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to evaluate the CGRP-mRNA expression and phosphorylated JNK (pJNK) protein in rat TG after the organ culture.

Results and Conclusions: The JNK inhibitor significantly reduced the organ culture and cytokines-induced up-regulation of CGRP-mRNA expression compared with control (P<0.05), indicating that a transcriptional mechanism was involved. Interestingly, the anti-migraine drug sumatriptan had similar effect. Western blotting showed that the cytokines significantly increased pJNK protein level, while this increase could decrease by sumatriptan and SP600125 (P<0.05), demonstrating that JNK mediated the up-regulation of CGRP expression induced by the cytokines. This may suggest a novel pharmacotherapeutical target for migraine treatment.

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