title: The impact of neuronal Notch-1/JNK pathway on intracerebral hemorrhage-induced neuronal injury of rat model.
abstract: Notch signaling is a highly conserved pathway that regulates cell fate decisions during embryonic development. Notch activation endangers neurons by modulating NF-κB and HIF-1α pathways, however, the role of Notch signaling in activating JNK/c-Jun following intracerebral hemorrhage (ICH) has not been investigated. In this study, we used rat ICH models and thrombin-induced cell models to investigate the potential role of Notch-1/JNK signals. Our findings revealed that Notch-1 and JNK increased in hematoma-surrounding neurons tissues following ICH during ischemic conditions (all p<0.05). Besides, the expression of active caspase-3 protein was also up-regulated after ICH. According to in-vitro assays, the expression of Notch-1, p-JNK, and active caspase-3 were all up-regulated in cell viability-decreasing ICH cell models (all p<0.05). However, blocking of either Notch-1 or JNK suppressed the phosphorylation of JNK and the expression of active caspase-3, and cell viability was obviously ameliorated. In conclusion, this work suggested Notch-1 activates JNK pathway to induce the active caspase-3, leading to neuronal injury when intracerebral hemorrhage or ischemia occurred. Thus the Notch-1/JNK signal pathway has an important role in ICH process, and may be a therapeutic target to prevent brain injury.
authors.affiliation: Department of Neurosurgery, Wenzhou Central Hospital, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, China.
authors.forename: Maohua
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Wenzhou Central Hospital, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Wenzhou Central Hospital, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Wenzhou Central Hospital, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, China.
authors.forename: Xiandong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Wenzhou Central Hospital, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, China.
authors.forename: Huajun
authors.initials: H
authors.lastname: Ba
authors.affiliation: Department of Neurosurgery, Wenzhou Central Hospital, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, China.
authors.forename: Qun
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Neurosurgery, Wenzhou Central Hospital, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Neurosurgery, Wenzhou Central Hospital, Affiliated Dingli Clinical Institute of Wenzhou Medical University, Wenzhou, China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D051881:Receptor, Notch1 / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052160:Benzothiazoles; D011743:Pyrimidines; D051881:Receptor, Notch1; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; C000609147:bentamapimod
keywords: ICH; JNK/c-Jun; Notch-1; Rat