title: Tetramethylpyrazine suppresses transient oxygen-glucose deprivation-induced connexin32 expression and cell apoptosis via the ERK1/2 and p38 MAPK pathway in cultured hippocampal neurons.
abstract: Tetramethylpyrazine (TMP) has been widely used in China as a drug for the treatment of various diseases. Recent studies have suggested that TMP has a protective effect on ischemic neuronal damage. However, the exact mechanism is still unclear. This study aims to investigate the mechanism of TMP mediated ischemic hippocampal neurons injury induced by oxygen-glucose deprivation (OGD). The effect of TMP on hippocampal neurons viability was detected by MTT assay, LDH release assay and apoptosis rate was measured by flow cytometry. TMP significantly suppressed neuron apoptosis in a concentration-dependent manner. TMP could significantly reduce the elevated levels of connexin32 (Cx32) induced by OGD. Knockdown of Cx32 by siRNA attenuated OGD injury. Moreover, our study showed that viability was increased in siRNA-Cx32-treated-neurons, and neuron apoptosis was suppressed by activating Bcl-2 expression and inhibiting Bax expression. Over expression of Cx32 could decrease neurons viability and increase LDH release. Furthermore, OGD increased phosphorylation of ERK1/2 and p38, whose inhibitors relieved the neuron injury and Cx32 up-regulation. Taken together, TMP can reverse the OGD-induced Cx32 expression and cell apoptosis via the ERK1/2 and p38 MAPK pathways.
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, Sichuan, China.
authors.forename: Gu
authors.initials: G
authors.lastname: Gong
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, Sichuan, China.
authors.forename: Libang
authors.initials: L
authors.lastname: Yuan
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, Sichuan, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, Sichuan, China.
authors.forename: Maorong
authors.initials: M
authors.lastname: Ran
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, Sichuan, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, Sichuan, China.
authors.forename: Huaqu
authors.initials: H
authors.lastname: Gong
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, Sichuan, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Anesthesia, General Hospital of Chengdu Military Area Command, Chengdu, Sichuan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Anesthesia, the Fourth Military Medical University Xijing Hospital, Xi'an, Shaanxi, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Dong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D011719:Pyrazines / Q000494:pharmacology*; D034622:RNA Interference; D017208:Rats, Wistar; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D005947:Glucose; D010100:Oxygen; D011719:Pyrazines; D000097002:Gap Junction beta-1 Protein; C017953:tetramethylpyrazine