title: Mitogen-activated protein kinase pathways are involved in the upregulation of calcitonin gene-related peptide of rat trigeminal ganglion after organ culture.
abstract: The trigeminal ganglion (TG) can express and release calcitonin gene-related peptide (CGRP), an important neuropeptide that plays a crucial role in migraine attack and cluster headache. Activation of rat TG increases CGRP expression. However, the regulatory mechanism of CGRP expression in TG neurons remains to be explored. This study aims to evaluate the involvement of mitogen-activated protein kinase (MAPK) pathways in CGRP upregulation after rat TG organ culture. Rat TG was cultured alone for 24 h or cultured in combination with MAPK inhibitors, tumor necrosis factor α (TNF-α), or interleukin 1β (IL-1β) for 24 h. CGRP protein was determined using immunohistochemistry. The mRNA levels of CGRP, TNF-α, and IL-1β were analyzed through real-time quantitative polymerase chain reaction. MAPK phosphorylation was detected via western blot. After rat TG organ culture, the expressions of CGRP, TNF-α, and IL-1β were upregulated at 24 h. The phosphorylation of extracellular signal-regulated kinases (ERK1/2), P38, and c-jun N-terminal kinases (JNK) significantly increased at 30 min compared with fresh rat TG. In addition, both CGRP expression and phosphorylation of ERK1/2, P38, and JNK were enhanced obviously after rat TG treatment with TNF-α or IL-1β compared with fresh rat TG. However, they decreased markedly after rat TG pretreatment with PD98059 (ERK1/2 inhibitor), SB203580 (P38 inhibitor), or SP600125 (JNK inhibitor) compared with rat TG co-culture with TNF-α or IL-1β. In conclusion, the elevated CGRP expression after rat TG organ culture can be regulated via MAPK pathways. The findings provide insight into the molecular mechanisms and experimental evidence for therapeutic targets of migraine.
authors.affiliation: Department of Genetics and Molecular Biology, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi, 710061, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Lei
authors.forename: Xingyun
authors.initials: X
authors.lastname: Yuan
authors.forename: Shaolan
authors.initials: S
authors.lastname: Wang
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Han
authors.forename: Qilan
authors.initials: Q
authors.lastname: Ning
authors.forename: Guogang
authors.initials: G
authors.lastname: Luo
authors.forename: Shemin
authors.initials: S
authors.lastname: Lu
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008881:Migraine Disorders / Q000188:drug therapy / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000873:Anthracenes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D053583:Interleukin-1beta; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015740:Calcitonin Gene-Related Peptide; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one