Isoflurane Postconditioning Upregulates Phosphorylated Connexin 43 in the Middle Cerebral Artery Occlusion Model and Is Probably Associated with the TGF-β1Smad23 Signaling Pathway
Joint Authors
Wang, Sheng
Yin, Jiangwen
Liu, Xuejiao
Wang, Ruixue
Ge, Mingyue
Xie, Liping
Zhai, Jingwen
Dai, Zhigang
Li, Yan
Source
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-03-17
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
Aim.
Connexin 43 (Cx43) has been identified to be important for cerebral ischemia/reperfusion (I/R) injury as well as protection from it.
This study was aimed at investigating the relationship between phosphorylated Cx43 (p-Cx43), transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling pathway, and isoflurane postconditioning (ISPOC), which has effects on brain injury in rats with cerebral ischemia/reperfusion (I/R) injury.
Methods.
The middle cerebral artery occlusion (MCAO) model was induced in 96 male Sprague-Dawley rats, weighing 250-300 g.
The rats were randomized into 12 groups, namely, sham, middle cerebral artery occlusion (MCAO)/I/R, I/R+1.5% ISPOC, I/R+LY2157299 (blocker of TGF-β1), I/R+LY2157299+1.5% ISPOC, I/R+Ro318220 (inhibitor of p-Cx43), I/R+Ro318220+1.5% ISPOC, I/R+18β-GA (activator of p-Cx43), I/R+18β-GA+1.5% ISPOC, I/R+1.5%ISPOC+LY2157299+Ro318220, dimethyl sulfoxide (DMSO), and 1.5% ISPOC+DMSO.
The protective effect of 1.5% ISPOC was tested by neurological deficit scoring and 2,3,5-triphenyl tetrazolium chloride staining (TTC staining).
The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method and hematoxylin-eosin (HE) staining were used to observe apoptosis of CA1 cells in the hippocampus.
The function of protein synthesis in neurons was tested by Nissl staining.
Expression levels of TGF-β1, Smad2/3, phosphorylated Smad2/3 (p-Smad2/3), Cx43, and phosphorylated Cx43 (p-Cx43) were measured by Western blot, immunofluorescence (IF), and quantitative real-time polymerase chain reaction (qRT-PCR).
Results.
Neurological deficit scores, brain infarct volume, and damaged neurons in the I/R group significantly increased compared to those in the sham group (P<0.05).
However, in the ISPOC group, damage of the brain was significantly ameliorated (P<0.05).
qRT-PCR showed more p-Cx43 mRNA expression in the hippocampal tissue of the ISPOC group than of the I/R group (P<0.05).
Western blot and immunofluorescence results showed similar changes in p-Cx43 protein levels of both groups.
The expression levels of related proteins (TGF-β1 and p-Smad2/3) both increased in the ISPOC group (P<0.05), whereas total Smad2/3 and total Cx43 expression did not change in all groups.
However, when a TGF-β1 inhibitor (LY2157299) was applied, expression levels of p-Cx43 significantly decreased as well as neuronal density (P<0.05).
By contrast, expression levels of TGF-β1 did not change significantly after the application of a p-Cx43 inhibitor (Ro318220) or the p-Cx43 activator 18β-GA (P>0.05).
Conclusion.
Isoflurane postconditioning (ISPOC) may alleviate cerebral I/R injury through upregulating the expression of p-Cx43, and the TGF-β1/Smad2/3 signaling pathway may be involved in the process.
American Psychological Association (APA)
Yin, Jiangwen& Liu, Xuejiao& Wang, Ruixue& Ge, Mingyue& Xie, Liping& Zhai, Jingwen…[et al.]. 2020. Isoflurane Postconditioning Upregulates Phosphorylated Connexin 43 in the Middle Cerebral Artery Occlusion Model and Is Probably Associated with the TGF-β1Smad23 Signaling Pathway. BioMed Research International،Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1133171
Modern Language Association (MLA)
Yin, Jiangwen…[et al.]. Isoflurane Postconditioning Upregulates Phosphorylated Connexin 43 in the Middle Cerebral Artery Occlusion Model and Is Probably Associated with the TGF-β1Smad23 Signaling Pathway. BioMed Research International No. 2020 (2020), pp.1-14.
https://search.emarefa.net/detail/BIM-1133171
American Medical Association (AMA)
Yin, Jiangwen& Liu, Xuejiao& Wang, Ruixue& Ge, Mingyue& Xie, Liping& Zhai, Jingwen…[et al.]. Isoflurane Postconditioning Upregulates Phosphorylated Connexin 43 in the Middle Cerebral Artery Occlusion Model and Is Probably Associated with the TGF-β1Smad23 Signaling Pathway. BioMed Research International. 2020. Vol. 2020, no. 2020, pp.1-14.
https://search.emarefa.net/detail/BIM-1133171
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1133171