PMID- 27693962
OWN - NLM
STAT- MEDLINE
DCOM- 20170213
LR  - 20200310
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 84
DP  - 2016 Dec
TI  - Effects of activin A and its downstream ERK1/2 in oxygen and glucose deprivation 
      after isoflurane-induced postconditioning.
PG  - 535-543
LID - S0753-3322(16)31047-2 [pii]
LID - 10.1016/j.biopha.2016.09.075 [doi]
AB  - BACKGROUND: Isoflurane postconditioning (ISPOC) plays a neuroprotection role in 
      the brain. Previous studies confirmed that isoflurane postconditioning can 
      provide better protection than preconditioning in acute hypoxic-ischemic brain 
      damage, such as acute craniocerebral trauma and ischemic stroke. Numerous studies 
      have reported that activin A can protect rat's brain from cell injury. However, 
      whether activin A and its downstream ERK1/2 were involved in isoflurane 
      postconditioning-induced neuroprotection is unknown. METHODS: A total of 80 
      healthy Sprague-Dawley rats weighing 50-70g were randomly divided into 10 groups 
      of 8: normal control, oxygen and glucose deprivation (OGD), 1.5% ISPOC, 3.0% 
      ISPOC, 4.5% ISPOC, blocker of activin A (SB431542), blocker of ERK1/2 (U0126), 
      3.0% ISPOC+SB431542, 3.0% ISPOC+U0126, and vehicle (dimethyl sulfoxide(DMSO)) 
      group. Blockers (SB431542 and U0126) were used in each concentration of 
      isoflurane before OGD. Hematoxylin-eosin staining, 2,3,5-triphenyl tetrazolium 
      chloride staining, and propidium iodide (PI) staining were conducted to assess 
      the reliability in the brain slices. Immunofluorescence, Western blot, and 
      quantitative real-time PCR(Q-PCR) were performed to validate the protein 
      expression levels of activin A, Smad2/3, P-Smad2/3, ERK1/2, and phosphorylation 
      ERK1/2 (P-ERK1/2). RESULTS: The number of damaged neurons and mean fluorescence 
      intensity(MFI) of PI staining increased, but formazan generation, expression 
      levels of activin A and P-ERK1/2 protein, and mRNA synthesis level of activin A 
      decreased in the OGD group compared with the normal control group (p<0.05). The 
      number of damaged neurons and MFI of PI staining decreased, but formazan 
      production, expression levels of activin A, P-Smad2/3, and P-ERK1/2, and mRNA 
      synthesis level of activin A increased significantly in the 1.5% ISPOC and 3.0% 
      ISPOC groups (p<0.05) compared with the OGD group. The result in the 4.5% ISPOC 
      group, was completely opposite to the 1.5% ISPOC and 3.0% ISPOC groups. The 
      number of damage neuron and MFI of PI staining increased, but formazan 
      production, expression levels of activin A, P-Smad2/3, and P-ERK1/2, and mRNA 
      synthesis level of activin A decreased in the 4.5% ISPOC group. However, the 
      expression levels of activin A, P-Smad2/3, and P-ERK1/2, and mRNA synthesis level 
      of activin A in the 4.5% ISPOC group were higher than the OGD group (p<0.05). The 
      other results were compared between the SB431542 group/the U0126 group and 3.0% 
      ISPOC group. The MFI of PI staining increased, but the expression levels of 
      activin A, P-Smad2/3, and P-ERK1/2 decreased (p<0.05). The expression level of 
      ERK1/2 protein in all groups exhibited no change (p>0.05). CONCLUSION: Results of 
      this study showed that 3.0% concentration of isoflurane postconditioning provided 
      better neuroprotection than 1.5% and 4.5% concentrations of isoflurane. Activin 
      A/Smad 2/3 and activin A/ERK1/2 signaling pathway may be involved in 
      ISPOC-induced neuroprotection.
CI  - Copyright (c) 2016 Elsevier Masson SAS. All rights reserved.
FAU - Wang, Qin
AU  - Wang Q
AD  - Department of Anesthesiology, First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi 832002, China. Electronic address: 313111941@qq.com.
FAU - Yin, Jiangwen
AU  - Yin J
AD  - Department of Anesthesiology, First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi 832002, China. Electronic address: 313111941@qq.com.
FAU - Wang, Sheng
AU  - Wang S
AD  - Department of Anesthesiology, First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi 832002, China. Electronic address: 
      iamsheng2006@163.com.
FAU - Cui, Di
AU  - Cui D
AD  - Department of Anesthesiology, First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi 832002, China.
FAU - Lin, Hong
AU  - Lin H
AD  - Department of Anesthesiology, First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi 832002, China.
FAU - Ge, Mingyue
AU  - Ge M
AD  - Department of Anesthesiology, First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi 832002, China.
FAU - Dai, Zhigang
AU  - Dai Z
AD  - Department of Anesthesiology, First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi 832002, China.
FAU - Xie, Liping
AU  - Xie L
AD  - Department of Anesthesiology, First Affiliated Hospital, School of Medicine, 
      Shihezi University, Shihezi 832002, China.
FAU - Si, Junqiang
AU  - Si J
AD  - Department of Physiology, School of Medicine, Shihezi University and the Key 
      Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi 832002, China.
FAU - Ma, Ketao
AU  - Ma K
AD  - Department of Physiology, School of Medicine, Shihezi University and the Key 
      Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi 832002, China.
FAU - Li, Li
AU  - Li L
AD  - Department of Physiology, School of Medicine, Shihezi University and the Key 
      Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi 832002, China.
FAU - Zhao, Lei
AU  - Zhao L
AD  - Department of Physiology, School of Medicine, Shihezi University and the Key 
      Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi 832002, China.
LA  - eng
PT  - Journal Article
DEP - 20160928
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Smad2 Protein)
RN  - 0 (Smad2 protein, rat)
RN  - 0 (Smad3 Protein)
RN  - 0 (Smad3 protein, rat)
RN  - 0 (inhibin beta A subunit)
RN  - 93443-12-0 (Inhibin-beta Subunits)
RN  - CYS9AKD70P (Isoflurane)
RN  - EC 2.7.11.24 (Mapk1 protein, rat)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia
MH  - Cell Survival/drug effects
MH  - Cytoprotection
MH  - Dose-Response Relationship, Drug
MH  - Glucose/deficiency
MH  - Hippocampus/*drug effects/enzymology/pathology
MH  - Hypoxia-Ischemia, Brain/enzymology/pathology/*prevention & control
MH  - In Vitro Techniques
MH  - Inhibin-beta Subunits/genetics/*metabolism
MH  - Isoflurane/*pharmacology
MH  - Mitogen-Activated Protein Kinase 1/*metabolism
MH  - Mitogen-Activated Protein Kinase 3/*metabolism
MH  - Nerve Degeneration
MH  - Neurons/*drug effects/enzymology/pathology
MH  - Neuroprotective Agents/*pharmacology
MH  - Phosphorylation
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/enzymology/pathology/*prevention & control
MH  - Signal Transduction/drug effects
MH  - Smad2 Protein/metabolism
MH  - Smad3 Protein/metabolism
MH  - Time Factors
OTO - NOTNLM
OT  - Activin A
OT  - Extracellular signal-regulated kinase 1/2
OT  - Hypoxic-ischemic brain damage
OT  - Isoflurane postconditioning
OT  - Oxygen and glucose deprivation
EDAT- 2016/10/04 06:00
MHDA- 2017/02/14 06:00
CRDT- 2016/10/04 06:00
PHST- 2016/07/12 00:00 [received]
PHST- 2016/09/17 00:00 [revised]
PHST- 2016/09/20 00:00 [accepted]
PHST- 2016/10/04 06:00 [pubmed]
PHST- 2017/02/14 06:00 [medline]
PHST- 2016/10/04 06:00 [entrez]
AID - S0753-3322(16)31047-2 [pii]
AID - 10.1016/j.biopha.2016.09.075 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2016 Dec;84:535-543. doi: 10.1016/j.biopha.2016.09.075. Epub 
      2016 Sep 28.