Wnt/Glycogen Synthase Kinase 3β/β-catenin Signaling Activation Mediated Sevoflurane Preconditioning-induced Cardioprotection
- Author:
- No author available
- Journal Title:
- Chinese Medical Journal
- Issue:
- 17
- DOI:
- 10.4103/0366-6999.163375
- Key Word:
- Cardioprotection;Ischemia-reperfusion Injury;Preconditioning;Sevoflurane;Wnt/Glycogen Synthase Kinase 3β/β-catenin Signaling
Abstract： Background:Sevoflurane preconditioning (SP) has been shown to invoke potent myocardial protection in animal studies and clinical trials.However,the mechanisms underlying SP are complex and not yet well understood.We investigated the hypothesis that the cardioprotection afforded by SP is mediated via the Wnt/glycogen synthase kinase 3β3 (GSK3β)/β-catenin signaling pathway.Methods:Two models were established:A Langendorffperfused rat heart model and the H9C2 cell hypoxia/reoxygenation model.Both rats and H9C2 cells were randomly divided into 6 groups as follows:S group,ischemia-reperfusion (I/R) group,DMSO group,IWP group,SP group,and SP + IWP group.Hemodynamic parameters,lactate dehydrogenase (LDH) activity in coronary effluent and cell culture supernatant,and the infarct size were measured to evaluate myocardial ischemia-reperfusion injuries.To determine the activity of Wnt/GSK3β/β-catenin signaling pathway,the expressions ofWnt3a,phospho-GSK3β,and β-catenin were measured by Western blotting.Results:SP improved cardiac function recovery,reduced infarct size (18 ± 2％ in the SP group compared with 35 ± 4％ in the I/R group;P ＜ 0.05),decreased LDH activity in coronary effluent,and culture supernatant.IWP-2,an inhibitor of Wnt,abolished the cardioprotection by SP.In addition,Western blotting analysis demonstrated that the expressions ofWnt3a,phospho-GSK3β,and β-catenin significantly (P ＜ 0.05) increased in the I/R group,compared with the S group;and compared to I/R group,SP significantly (P ＜ 0.05) increased Wnt3a,phospho-GSK3β,and β-catenin expressions.Pretreatment with IWP-2 significantly (P ＜ 0.05) abolished SP-induced Wnt/GSK3 β/β-catenin signaling activation.Conclusions:The results showed for the first time that cardioprotection afforded by SP may be mediated partly via the Wnt/GSK3β/β-catenin signaling pathway.
- [1]A, Wodarz,R, Nusse.Mechanisms of Wnt signaling in development.[J].1998,14.
- [2]Z Z, Chong,K, Maiese.Targeting WNT, protein kinase B, and mitochondrial membrane integrity to foster cellular survival in the nervous system.[J].2004,19.
- [3]Zaugg M,Schaub MC,Roschitzki B,etc.Phosphoproteome analysis of isoflurane-protected heart mitochondria: phosphorylation of adenine nucleotide translocator-1 on Tyr194 regulates mitochondrial function.[J].2008,80(1).
- [4]Yan Ni, Loh,Ellen L, Hedditch,Laura A, Baker,etc.The Wnt signalling pathway is upregulated in an in vitro model of acquired tamoxifen resistant breast cancer.[J].2013,13.
- [5]Hovsep S. Melkonyan,Wei C. Chang,John P. Shapiro.SARPs: A family of secreted apoptosis-related proteins[J].1997,94(25).
- [6]Koichi, Inagaki,Rebecca, Begley,Fumiaki, Ikeno,etc.Cardioprotection by epsilon-protein kinase C activation from ischemia: continuous delivery and antiarrhythmic effect of an epsilon-protein kinase C-activating peptide.[J].2005,111.
- [7]Paul S, Pagel,John G, Krolikowski,Donald A, Neff,etc.Inhibition of glycogen synthase kinase enhances isoflurane-induced protection against myocardial infarction during early reperfusion in vivo.[J].2006,102.
- [8]Mirotsou M,Zhang LN,Gnecchi M,etc.Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair[J].2007,104(5).
- [9]Gomez L,Paillard M,Thibault H,etc.Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion.[J].2008,117(21).
- [10]Min Park,ByungSoo Youn,Xi-long Zheng,etc.Globular Adiponectin, Acting via AdipoR1/APPL1, Protects H9c2 Cells from Hypoxia/Reoxygenation-Induced Apoptosis.[J].2011,6(4).
- [11]Giuseppina, Milano,Sandrine, Morel,Christophe, Bonny,etc.A peptide inhibitor of c-Jun NH2-terminal kinase reduces myocardial ischemia-reperfusion injury and infarct size in vivo.[J].2007,292(4).
- [12]Zheng XL,Shin EJ,Schram K.Leptin attenuates hypoxia/reoxygenation-induced activation of the intrinsic pathway of apoptosis in rat H9c2 cells.[J].2009,221(2).
- [13]Haiyan, Tong,Kenichi, Imahashi,Charles, Steenbergen,etc.Phosphorylation of glycogen synthase kinase-3beta during preconditioning through a phosphatidylinositol-3-kinase--dependent pathway is cardioprotective.[J].2002,90.
- [14]R A, Cavallo,R T, Cox,M M, Moline,etc.Drosophila Tcf and Groucho interact to repress Wingless signalling activity.[J].1998,395(6702).
- [15]Xi L,Kukreja RC,Das A.Protein Kinase G-dependent Cardioprotective Mechanism of Phosphodiesterase-5 Inhibition Involves Phosphorylation of ERK and GSK3 beta[J].2008,283(43).
- [16]An-lu DAI,Li-hua FAN,Feng-jiang ZHANG,etc.Effects of sevoflurane preconditioning and postconditioning on rat myocardial stunning in ischemic reperfusion injury[J].2010,(4).
- [17]Chong ZZ,Li F,Maiese K.Winding through the WNT pathway during cellular development and demise.[J].2006,21(1).
- [18]Hans, Clevers.Wnt/beta-catenin signaling in development and disease.[J].2006,127.
- [19]Yin H,Chao L,Chao J.Adrenomedullin protects against myocardial apoptosis after ischemia/reperfusion through activation of Akt-GSK signaling.[J].2004,43(1).
- [20]Dale TC,Smalley MJ.Wnt signalling in mammalian development and cancer.[J].1999,18(2).
- [21]Bao,Weike.Inhibition of Rho-kinase protects the heart against ischemia/reperfusion injury.[J].2004,61(3).
- [22]Li XX,Bian HJ,Zhang J,etc.Inhibition of the activity of Rho-kinase reduces cardiomyocyte apoptosis in heart ischemia/reperfusion via suppressing JNK-mediated AIF translocation.[J].2009,401(1).
- [23]Weinbrenner C,Wagner C,Strasser RH,etc.Cardioprotection by postconditioning is lost in WOKW rats with metabolic syndrome: role of glycogen synthase kinase 3beta.[J].2008,52(5).
- [24]Bauer A.,Kispert A.,Kemler R.,etc.Beta-Catenin is a Target for the Ubiquitin-Proteasome Pathway[J].1997,16(13).
- [25]Murphy,E,Steenbergen,C.Preconditioning: the mitochondrial connection.[J].2007,69.
- [26]Maralice, Conacci-Sorrell,Jacob, Zhurinsky,Avri, Ben-Ze'ev.The cadherin-catenin adhesion system in signaling and cancer.[J].2002,109(8).
- [27]Lipton, S. A.,Bossy-Wetzel, E..Dueling Activities of AIF in Cell Death versus Survival: DNA Binding and Redox Activity[J].2002,111(2).
- [28]R A, Kloner,R, Bolli,E, Marban,etc.Medical and cellular implications of stunning, hibernation, and preconditioning: an NHLBI workshop.[J].1998,97.
- [29]N C, Weber,W, Schlack.Inhalational anaesthetics and cardioprotection.[J].2008,(182).
- [30]Wang J,Rezaie AR,Yang L,etc.Activated protein C protects against myocardial ischemic/reperfusion injury through AMP-activated protein kinase signaling.[J].2011,9(7).
- [31]R, Nusse,H E, Varmus.Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome.[J].1982,31(1).
- [32]Pascal C, Chiari,Martin W, Bienengraeber,Paul S, Pagel,etc.Isoflurane protects against myocardial infarction during early reperfusion by activation of phosphatidylinositol-3-kinase signal transduction: evidence for anesthetic-induced postconditioning in rabbits.[J].2005,102.
- [33]J, Roose,M, Molenaar,J, Peterson,etc.The Xenopus Wnt effector XTcf-3 interacts with Groucho-related transcriptional repressors.[J].1998,395(6702).
- [34]Bienengraeber M,Warltier DC,Krolikowski JG,etc.Role of Erk1/2, p70s6K, and eNOS in isoflurane-induced cardioprotection during early reperfusion in vivo: (Le role des Erk1/2, p70s6K et eNOS dans la cardioprotection induite par l'isoflurane pendant la reperfusion in vivo precoce).[J].2006,53(2).
- [35]Laurent, Barandon,Pascale, Dufourcq,Pierre, Costet,etc.Involvement of FrzA/sFRP-1 and the Wnt/frizzled pathway in ischemic preconditioning.[J].2005,96.
- [36]McShane-Kay K,Danielsen CA,Mbuy GK,etc.Herpes simplex virus-type 2 infectivity and agents that block gap junctional intercellular communication.[J].2007,124(1).
- [37]Kariya T,Fujiwara T,Fujiwara H,etc.Cross-talk among noradrenaline, adenosine and protein kinase C in the mechanisms of ischemic preconditioning in rabbits.[J].2003,41(Suppl.1).
- [38]Patapoutian A,Reichardt LF.Roles of Wnt proteins in neural development and maintenance.[J].2000,10(3).
- [39]C E, Murry,R B, Jennings,K A, Reimer.Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.[J].1986,74.
- [40]R A, Hopper,C R, Forrest,H, Xu,etc.Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction.[J].2000,279(2).