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Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction

Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction. This present study examined the effect of a plant-derived flavone tangeretin (TG) on autophagy and reduction in myocardial dysfunction. The sepsis was induced by cecum ligation and p...

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Autores principales: Shiroorkar, Predeepkumar Narayanappa, Afzal, Obaid, Kazmi, Imran, Al-Abbasi, Fahad A., Altamimi, Abdulmalik Saleh Alfawaz, Gubbiyappa, Kumar Shiva, Sreeharsha, Nagaraja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729459/
https://www.ncbi.nlm.nih.gov/pubmed/33260422
http://dx.doi.org/10.3390/molecules25235622
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author Shiroorkar, Predeepkumar Narayanappa
Afzal, Obaid
Kazmi, Imran
Al-Abbasi, Fahad A.
Altamimi, Abdulmalik Saleh Alfawaz
Gubbiyappa, Kumar Shiva
Sreeharsha, Nagaraja
author_facet Shiroorkar, Predeepkumar Narayanappa
Afzal, Obaid
Kazmi, Imran
Al-Abbasi, Fahad A.
Altamimi, Abdulmalik Saleh Alfawaz
Gubbiyappa, Kumar Shiva
Sreeharsha, Nagaraja
author_sort Shiroorkar, Predeepkumar Narayanappa
collection PubMed
description Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction. This present study examined the effect of a plant-derived flavone tangeretin (TG) on autophagy and reduction in myocardial dysfunction. The sepsis was induced by cecum ligation and puncture (CLP) in male Sprague–Dawley rats. Abnormal changes were seen in the heart after the sepsis induction. These abnormalities were analyzed based on the cardiac markers, namely Cardiac myosin light chain-1 (cMLC1) and Cardiac troponin I (cTnl), echocardiography, and plasma parameters, like Lactate dehydrogenase (LDH) and Creatinine kinase (CK). Microanatomy of the heart was studied using hematoxylin and eosin stained histopathological samples of cardiac tissue. Western blot technique was used to detect the nature and extent of protein with the amount of a specific RNA (gene expression) in the cardiac homogenate. Oxidative damage was analyzed using redox marker, reduced glutathione. This study successfully showed that TG attenuated sepsis-induced myocardial dysfunction by inhibiting myocardial autophagy via silencing the Phosphatase and tensin homolog (PTEN) expression and acting on the AKT/mTOR pathway. The present findings supported that TG is a novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction.
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spelling pubmed-77294592020-12-12 Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction Shiroorkar, Predeepkumar Narayanappa Afzal, Obaid Kazmi, Imran Al-Abbasi, Fahad A. Altamimi, Abdulmalik Saleh Alfawaz Gubbiyappa, Kumar Shiva Sreeharsha, Nagaraja Molecules Article Sepsis aggregates undesirable immune response causing depression of ventricular myocardium and diastolic dysfunction. This present study examined the effect of a plant-derived flavone tangeretin (TG) on autophagy and reduction in myocardial dysfunction. The sepsis was induced by cecum ligation and puncture (CLP) in male Sprague–Dawley rats. Abnormal changes were seen in the heart after the sepsis induction. These abnormalities were analyzed based on the cardiac markers, namely Cardiac myosin light chain-1 (cMLC1) and Cardiac troponin I (cTnl), echocardiography, and plasma parameters, like Lactate dehydrogenase (LDH) and Creatinine kinase (CK). Microanatomy of the heart was studied using hematoxylin and eosin stained histopathological samples of cardiac tissue. Western blot technique was used to detect the nature and extent of protein with the amount of a specific RNA (gene expression) in the cardiac homogenate. Oxidative damage was analyzed using redox marker, reduced glutathione. This study successfully showed that TG attenuated sepsis-induced myocardial dysfunction by inhibiting myocardial autophagy via silencing the Phosphatase and tensin homolog (PTEN) expression and acting on the AKT/mTOR pathway. The present findings supported that TG is a novel cardioprotective therapeutic target for sepsis induced myocardial dysfunction. MDPI 2020-11-29 /pmc/articles/PMC7729459/ /pubmed/33260422 http://dx.doi.org/10.3390/molecules25235622 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Shiroorkar, Predeepkumar Narayanappa
Afzal, Obaid
Kazmi, Imran
Al-Abbasi, Fahad A.
Altamimi, Abdulmalik Saleh Alfawaz
Gubbiyappa, Kumar Shiva
Sreeharsha, Nagaraja
Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction
title Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction
title_full Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction
title_fullStr Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction
title_full_unstemmed Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction
title_short Cardioprotective Effect of Tangeretin by Inhibiting PTEN/AKT/mTOR Axis in Experimental Sepsis-Induced Myocardial Dysfunction
title_sort cardioprotective effect of tangeretin by inhibiting pten/akt/mtor axis in experimental sepsis-induced myocardial dysfunction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729459/
https://www.ncbi.nlm.nih.gov/pubmed/33260422
http://dx.doi.org/10.3390/molecules25235622
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