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We are analyzing https://link.springer.com/article/10.1186/s12933-014-0132-9.

Title:
Exendin-4 ameliorates cardiac ischemia/reperfusion injury via caveolae and caveolins-3 | Cardiovascular Diabetology
Description:
Background Exendin-4, an exogenous glucagon-like peptide-1 receptor (GLP-1R) agonist, protects the heart from ischemia/reperfusion injury. However, the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for exendin-4 induced cardiac protection using in vitro and in vivo studies in control and caveolin-3 (Cav-3) knockout mice (Cav-3 KO). Methods Myocytes were treated with exendin-4 and then incubated with methyl-β-cyclodextrin (MβCD) to disrupt caveolae formation. This was then followed by simulated ischemia/reperfusion (SI/R). In addition, cardiac protection in vivo was assessed by measuring infarct size and cardiac troponin levels. Results Exendin-4 protected cardiac myocytes (CM) from SI/R [35.6 ± 12.6% vs. 64.4 ± 18.0% cell death, P = 0.034] and apoptosis but this protection was abolished by MβCD (71.8 ± 10.8% cell death, P = 0.004). Furthermore, Cav-3/GLP-1R co-localization was observed and membrane fractionation by sucrose density gradient centrifugation of CM treated with MβCD  + exendin-4 revealed that buoyant (caveolae enriched) fractions decreased Cav-3 compared to CM treated with exendin-4 exclusively. Furthermore, exendin-4 induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 25.1 ± 8.2% vs. 41.4 ± 4.1%, P < 0.001; troponin: 36.9 ± 14.2 vs. 101.1 ± 22.3 ng/ml, P < 0.001). However, exendin-4 induced cardiac protection was abolished in Cav-3 KO mice (infarct size: 43.0 ± 6.4%, P < 0.001; troponin: 96.8 ± 26.6 ng/ml, P = 0.001). Conclusions We conclude that caveolae and caveolin-3 are critical for exendin-4 induced protection of the heart from ischemia/reperfusion injury.
Website Age:
28 years and 1 months (reg. 1997-05-29).

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🌠 Phenomenal Traffic: 5M - 10M visitors per month


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Keywords {🔍}

pubmed, article, cardiac, google, scholar, cav, glp, cas, protection, ischemiareperfusion, caveolae, mice, glpr, exendin, injury, tsutsumi, heart, figure, size, peptide, receptor, control, sir, cell, membrane, caveolin, glucagonlike, induced, expression, caveolins, central, myocytes, mβcd, myocardial, patel, vivo, infarct, death, effects, fractions, cells, diabetes, vitro, min, media, incubated, effect, rate, pressure, authors,

Topics {✒️}

g-protein-coupled receptor-signaling components o-linked beta-n-acetylglucosamine g-protein-coupled receptor noyan-ashraf mh article download pdf 12 hour light dark cycle argon-krypton laser source glp-1r-protein kinase myocardial ischaemia-reperfusion injury mikro-tip pressure transducer anti-apoptotic gene expression full size image targeting pro-survival signaling bonferroni post-hoc test isoflurane-induced cardiac protection myocardial ischemia/reperfusion injury membrane potential-sensitive dye rodents lacking glp-1r anti-apoptosis gene expression open access license central nervous system glp-1-induced cardiac protection methyl-β-cyclodextrin si/ signaling molecules including extracellular regulated kinases central nervous effects contra-regulatory response investigated ischemia/reperfusion injury reporting animal research vitro simulated ischemia/reperfusion nutrient-dependent manner methyl-β-cyclodextrin wild-type mice compared intestinal hormone secreted glp-1r knockout mice glp-1r dependent effects wild-type mice treated full access ad lib access hypoxia-induced cell death experimental myocardial infarction privacy choices/manage cookies authors’ original file caveolin-binding motif [11]-[13] caveolin-binding motifs glp-1r activation article tsutsumi cav-1 binding domain localize molecules involved myocardial infarct size

Schema {🗺️}

WebPage:
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         headline:Exendin-4 ameliorates cardiac ischemia/reperfusion injury via caveolae and caveolins-3
         description:Exendin-4, an exogenous glucagon-like peptide-1 receptor (GLP-1R) agonist, protects the heart from ischemia/reperfusion injury. However, the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for exendin-4 induced cardiac protection using in vitro and in vivo studies in control and caveolin-3 (Cav-3) knockout mice (Cav-3 KO). Myocytes were treated with exendin-4 and then incubated with methyl-β-cyclodextrin (MβCD) to disrupt caveolae formation. This was then followed by simulated ischemia/reperfusion (SI/R). In addition, cardiac protection in vivo was assessed by measuring infarct size and cardiac troponin levels. Exendin-4 protected cardiac myocytes (CM) from SI/R [35.6 ± 12.6% vs. 64.4 ± 18.0% cell death, P = 0.034] and apoptosis but this protection was abolished by MβCD (71.8 ± 10.8% cell death, P = 0.004). Furthermore, Cav-3/GLP-1R co-localization was observed and membrane fractionation by sucrose density gradient centrifugation of CM treated with MβCD  + exendin-4 revealed that buoyant (caveolae enriched) fractions decreased Cav-3 compared to CM treated with exendin-4 exclusively. Furthermore, exendin-4 induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 25.1 ± 8.2% vs. 41.4 ± 4.1%, P &lt; 0.001; troponin: 36.9 ± 14.2 vs. 101.1 ± 22.3 ng/ml, P &lt; 0.001). However, exendin-4 induced cardiac protection was abolished in Cav-3 KO mice (infarct size: 43.0 ± 6.4%, P &lt; 0.001; troponin: 96.8 ± 26.6 ng/ml, P = 0.001). We conclude that caveolae and caveolin-3 are critical for exendin-4 induced protection of the heart from ischemia/reperfusion injury.
         datePublished:2014-09-07T00:00:00Z
         dateModified:2014-09-07T00:00:00Z
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         sameAs:https://doi.org/10.1186/s12933-014-0132-9
         keywords:
            Cardiac protection
            Subcellular microdomain
            Glucagon-like peptide-1 receptor
            Incretin
            Diabetes
            Angiology
            Cardiology
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      headline:Exendin-4 ameliorates cardiac ischemia/reperfusion injury via caveolae and caveolins-3
      description:Exendin-4, an exogenous glucagon-like peptide-1 receptor (GLP-1R) agonist, protects the heart from ischemia/reperfusion injury. However, the mechanisms for this protection are poorly understood. Caveolae, sarcolemmal invaginations, and caveolins, scaffolding proteins in caveolae, localize molecules involved in cardiac protection. We tested the hypothesis that caveolae and caveolins are essential for exendin-4 induced cardiac protection using in vitro and in vivo studies in control and caveolin-3 (Cav-3) knockout mice (Cav-3 KO). Myocytes were treated with exendin-4 and then incubated with methyl-β-cyclodextrin (MβCD) to disrupt caveolae formation. This was then followed by simulated ischemia/reperfusion (SI/R). In addition, cardiac protection in vivo was assessed by measuring infarct size and cardiac troponin levels. Exendin-4 protected cardiac myocytes (CM) from SI/R [35.6 ± 12.6% vs. 64.4 ± 18.0% cell death, P = 0.034] and apoptosis but this protection was abolished by MβCD (71.8 ± 10.8% cell death, P = 0.004). Furthermore, Cav-3/GLP-1R co-localization was observed and membrane fractionation by sucrose density gradient centrifugation of CM treated with MβCD  + exendin-4 revealed that buoyant (caveolae enriched) fractions decreased Cav-3 compared to CM treated with exendin-4 exclusively. Furthermore, exendin-4 induced a reduction in infarct size and cardiac troponin relative to control (infarct size: 25.1 ± 8.2% vs. 41.4 ± 4.1%, P &lt; 0.001; troponin: 36.9 ± 14.2 vs. 101.1 ± 22.3 ng/ml, P &lt; 0.001). However, exendin-4 induced cardiac protection was abolished in Cav-3 KO mice (infarct size: 43.0 ± 6.4%, P &lt; 0.001; troponin: 96.8 ± 26.6 ng/ml, P = 0.001). We conclude that caveolae and caveolin-3 are critical for exendin-4 induced protection of the heart from ischemia/reperfusion injury.
      datePublished:2014-09-07T00:00:00Z
      dateModified:2014-09-07T00:00:00Z
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      license:http://creativecommons.org/publicdomain/zero/1.0/
      sameAs:https://doi.org/10.1186/s12933-014-0132-9
      keywords:
         Cardiac protection
         Subcellular microdomain
         Glucagon-like peptide-1 receptor
         Incretin
         Diabetes
         Angiology
         Cardiology
      image:
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                     type:PostalAddress
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                  address:
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            address:
               name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
               type:PostalAddress
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      name:Rie Tsutsumi
      affiliation:
            name:University of Tokushima
            address:
               name:Department of Nutrition, University of Tokushima, Tokushima, Japan
               type:PostalAddress
            type:Organization
      name:Eisuke Hamaguchi
      affiliation:
            name:University of Tokushima
            address:
               name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
               type:PostalAddress
            type:Organization
      name:Yoko Sakai
      affiliation:
            name:University of Tokushima
            address:
               name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
               type:PostalAddress
            type:Organization
      name:Asuka Kasai
      affiliation:
            name:University of Tokushima
            address:
               name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
               type:PostalAddress
            type:Organization
      name:Yoshihiro Ishikawa
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      name:Utako Yokoyama
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            address:
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               type:PostalAddress
            type:Organization
      name:Katsuya Tanaka
      affiliation:
            name:University of Tokushima
            address:
               name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
      name:Department of Nutrition, University of Tokushima, Tokushima, Japan
      name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
      name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
      name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan
      name:Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan
      name:Cardiovascular Research Institute, Yokohama City University, Yokohama, Japan
      name:Department of Anesthesiology, University of Tokushima, Kuramoto, Tokushima, Japan

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