Isoflurane Postconditioning Upregulates Phosphorylated Connexin 43 in the Middle Cerebral Artery Occlusion Model and Is Probably Associated with the TGF-β1/Smad2/3 Signaling Pathway.
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...
| Published in: | BioMed Research International pp. 1 - 15 |
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| Main Authors: | , , , , , , , , |
| Format: | pictorial research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
3/17/2020
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=142387462&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 142387462 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 23146133 FT2T jtl: BioMed Research International issn: 23146133 maglogo: N pubinfo: dt: 3/17/2020 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 142387462 142387462 142387462 10.1155/2020/3451215 142387462 ppf: 1 ppct: 14 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Isoflurane Postconditioning Upregulates Phosphorylated Connexin 43 in the Middle Cerebral Artery Occlusion Model and Is Probably Associated with the TGF-β1/Smad2/3 Signaling Pathway. aug: au: Yin, Jiangwen Liu, Xuejiao Wang, Ruixue Ge, Mingyue Xie, Liping Zhai, Jingwen Dai, Zhigang Li, Yan Wang, Sheng affil: Department of Anesthesiology, First Affiliated Hospital, School of Medicine, Shihezi University, Shihezi 832002, China sug: subj: Middle Cerebral Artery Pathology Cerebral Ischemia Drug Therapy Ischemic Preconditioning Isoflurane Pharmacodynamics Phosphorylation Drug Effects Connexins Therapeutic Use Signal Transduction Drug Effects Reperfusion Injury Drug Therapy Animal Studies Rats Staining and Labeling Methods Apoptosis Drug Effects Blotting, Western Fluorescent Antibody Technique Polymerase Chain Reaction Hippocampus Drug Effects Neurons Drug Effects ab: 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. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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