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Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes

Cardiac cells can adapt to pathological stress-induced energy crisis by shifting from fatty acid oxidation to glycolysis. However, the use of glucose-insulin-potassium (GIK) solution in patients undergoing cardiac surgery does not alleviate ischemia/reperfusion (I/R)-induced energy shortage. This in...

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Autores principales: Essandoh, Kobina, Deng, Shan, Wang, Xiaohong, Li, Yutian, Li, Qianqian, Mu, Xingjiang, Peng, Tianqing, Fan, Guo-Chang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565110/
https://www.ncbi.nlm.nih.gov/pubmed/32839388
http://dx.doi.org/10.3390/cells9091936
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author Essandoh, Kobina
Deng, Shan
Wang, Xiaohong
Li, Yutian
Li, Qianqian
Mu, Xingjiang
Peng, Tianqing
Fan, Guo-Chang
author_facet Essandoh, Kobina
Deng, Shan
Wang, Xiaohong
Li, Yutian
Li, Qianqian
Mu, Xingjiang
Peng, Tianqing
Fan, Guo-Chang
author_sort Essandoh, Kobina
collection PubMed
description Cardiac cells can adapt to pathological stress-induced energy crisis by shifting from fatty acid oxidation to glycolysis. However, the use of glucose-insulin-potassium (GIK) solution in patients undergoing cardiac surgery does not alleviate ischemia/reperfusion (I/R)-induced energy shortage. This indicates that insulin-mediated translocation of glucose transporter-4 (Glut-4) is impaired in ischemic hearts. Indeed, cardiac myocytes contain two intracellular populations of Glut-4: an insulin-dependent non-endosomal pool (also referred to as Glut-4 storage vesicles, GSVs) and an insulin-independent endosomal pool. Tumor susceptibility gene 101 (Tsg101) has been implicated in the endosomal recycling of membrane proteins. In this study, we aimed to examine whether Tsg101 regulated the sorting and re-distribution of Glut-4 to the sarcolemma membrane of cardiomyocytes under basal and ischemic conditions, using gain- and loss-of-function approaches. Forced overexpression of Tsg101 in mouse hearts and isolated cardiomyocytes could promote Glut-4 re-distribution to the sarcolemma, leading to enhanced glucose entry and adenosine triphosphate (ATP) generation in I/R hearts which in turn, attenuation of I/R-induced cardiac dysfunction. Conversely, knockdown of Tsg101 in cardiac myocytes exhibited opposite effects. Mechanistically, we identified that Tsg101 could interact and co-localize with Glut-4 in the sarcolemma membrane of cardiomyocytes. Our findings define Tsg101 as a novel regulator of cardiac Glut-4 trafficking, which may provide a new therapeutic strategy for the treatment of ischemic heart disease.
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spelling pubmed-75651102020-10-26 Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes Essandoh, Kobina Deng, Shan Wang, Xiaohong Li, Yutian Li, Qianqian Mu, Xingjiang Peng, Tianqing Fan, Guo-Chang Cells Article Cardiac cells can adapt to pathological stress-induced energy crisis by shifting from fatty acid oxidation to glycolysis. However, the use of glucose-insulin-potassium (GIK) solution in patients undergoing cardiac surgery does not alleviate ischemia/reperfusion (I/R)-induced energy shortage. This indicates that insulin-mediated translocation of glucose transporter-4 (Glut-4) is impaired in ischemic hearts. Indeed, cardiac myocytes contain two intracellular populations of Glut-4: an insulin-dependent non-endosomal pool (also referred to as Glut-4 storage vesicles, GSVs) and an insulin-independent endosomal pool. Tumor susceptibility gene 101 (Tsg101) has been implicated in the endosomal recycling of membrane proteins. In this study, we aimed to examine whether Tsg101 regulated the sorting and re-distribution of Glut-4 to the sarcolemma membrane of cardiomyocytes under basal and ischemic conditions, using gain- and loss-of-function approaches. Forced overexpression of Tsg101 in mouse hearts and isolated cardiomyocytes could promote Glut-4 re-distribution to the sarcolemma, leading to enhanced glucose entry and adenosine triphosphate (ATP) generation in I/R hearts which in turn, attenuation of I/R-induced cardiac dysfunction. Conversely, knockdown of Tsg101 in cardiac myocytes exhibited opposite effects. Mechanistically, we identified that Tsg101 could interact and co-localize with Glut-4 in the sarcolemma membrane of cardiomyocytes. Our findings define Tsg101 as a novel regulator of cardiac Glut-4 trafficking, which may provide a new therapeutic strategy for the treatment of ischemic heart disease. MDPI 2020-08-21 /pmc/articles/PMC7565110/ /pubmed/32839388 http://dx.doi.org/10.3390/cells9091936 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
Essandoh, Kobina
Deng, Shan
Wang, Xiaohong
Li, Yutian
Li, Qianqian
Mu, Xingjiang
Peng, Tianqing
Fan, Guo-Chang
Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes
title Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes
title_full Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes
title_fullStr Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes
title_full_unstemmed Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes
title_short Tsg101 Is Involved in the Sorting and Re-Distribution of Glucose Transporter-4 to the Sarcolemma Membrane of Cardiac Myocytes
title_sort tsg101 is involved in the sorting and re-distribution of glucose transporter-4 to the sarcolemma membrane of cardiac myocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565110/
https://www.ncbi.nlm.nih.gov/pubmed/32839388
http://dx.doi.org/10.3390/cells9091936
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