PMID- 25237906
OWN - NLM
STAT- MEDLINE
DCOM- 20150616
LR  - 20231213
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 9
DP  - 2014
TI  - Tetramethylpyrazine suppresses transient oxygen-glucose deprivation-induced 
      connexin32 expression and cell apoptosis via the ERK1/2 and p38 MAPK pathway in 
      cultured hippocampal neurons.
PG  - e105944
LID - 10.1371/journal.pone.0105944 [doi]
LID - e105944
AB  - 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.
FAU - Gong, Gu
AU  - Gong G
AD  - Department of Anesthesia, General Hospital of Chengdu Military Area Command, 
      Chengdu, Sichuan, China.
FAU - Yuan, Libang
AU  - Yuan L
AD  - Department of Anesthesia, General Hospital of Chengdu Military Area Command, 
      Chengdu, Sichuan, China.
FAU - Cai, Lin
AU  - Cai L
AD  - Department of Anesthesia, General Hospital of Chengdu Military Area Command, 
      Chengdu, Sichuan, China.
FAU - Ran, Maorong
AU  - Ran M
AD  - Department of Anesthesia, General Hospital of Chengdu Military Area Command, 
      Chengdu, Sichuan, China.
FAU - Zhang, Yulan
AU  - Zhang Y
AD  - Department of Anesthesia, General Hospital of Chengdu Military Area Command, 
      Chengdu, Sichuan, China.
FAU - Gong, Huaqu
AU  - Gong H
AD  - Department of Anesthesia, General Hospital of Chengdu Military Area Command, 
      Chengdu, Sichuan, China.
FAU - Dai, Xuemei
AU  - Dai X
AD  - Department of Anesthesia, General Hospital of Chengdu Military Area Command, 
      Chengdu, Sichuan, China.
FAU - Wu, Wei
AU  - Wu W
AD  - Department of Anesthesia, General Hospital of Chengdu Military Area Command, 
      Chengdu, Sichuan, China.
FAU - Dong, Hailong
AU  - Dong H
AD  - Department of Anesthesia, the Fourth Military Medical University Xijing Hospital, 
      Xi'an, Shaanxi, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140919
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Connexins)
RN  - 0 (Pyrazines)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
RN  - V80F4IA5XG (tetramethylpyrazine)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Cells, Cultured
MH  - Connexins/genetics/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Gene Knockdown Techniques
MH  - Glucose/*metabolism
MH  - Hippocampus/cytology/*drug effects
MH  - MAP Kinase Signaling System/drug effects
MH  - Neurons/*drug effects
MH  - Oxygen/*metabolism
MH  - Phosphorylation
MH  - Pyrazines/*pharmacology
MH  - RNA Interference
MH  - Rats, Wistar
MH  - Gap Junction beta-1 Protein
PMC - PMC4169508
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/09/23 06:00
MHDA- 2015/06/17 06:00
PMCR- 2014/09/19
CRDT- 2014/09/20 06:00
PHST- 2014/02/06 00:00 [received]
PHST- 2014/07/29 00:00 [accepted]
PHST- 2014/09/20 06:00 [entrez]
PHST- 2014/09/23 06:00 [pubmed]
PHST- 2015/06/17 06:00 [medline]
PHST- 2014/09/19 00:00 [pmc-release]
AID - PONE-D-14-04053 [pii]
AID - 10.1371/journal.pone.0105944 [doi]
PST - epublish
SO  - PLoS One. 2014 Sep 19;9(9):e105944. doi: 10.1371/journal.pone.0105944. 
      eCollection 2014.