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Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway
METHODS: Rat neonate cardiomyocytes were cultured and treated with AGEs at different concentration. Two classic autophagy markers, microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinas...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998738/ https://www.ncbi.nlm.nih.gov/pubmed/24725502 http://dx.doi.org/10.1186/1475-2840-13-78 |
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author | Hou, Xuwei Hu, Zhaohui Xu, Hanying Xu, Jian Zhang, Shunrong Zhong, Yigang He, Xiuying Wang, Ningfu |
author_facet | Hou, Xuwei Hu, Zhaohui Xu, Hanying Xu, Jian Zhang, Shunrong Zhong, Yigang He, Xiuying Wang, Ningfu |
author_sort | Hou, Xuwei |
collection | PubMed |
description | METHODS: Rat neonate cardiomyocytes were cultured and treated with AGEs at different concentration. Two classic autophagy markers, microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mTOR pathway were applied to cells, respectively. RESULTS: AGEs administration enhanced the expression of Beclin-1 and LC3 II in cardiomyocytes, increased the number of autophagic vacuoles and impaired the cell viability in dose-dependant manners. Also, AGEs inhibited the PI3K/Akt/mTOR pathway via RAGE. Inhibition of RAGE with RAGE antibody reduced expression of Beclin-1 and LC3 II/I and inhibited the cellular autophagy, accompanied by the reactivation of PI3K/Akt/mTOR pathway in cultured cells. Notably, the presence of inhibition of PI3K/Akt/mTOR pathway abolished the protective effect of RAGE inhibition on cardiomyocytes. CONCLUSION: This study provides evidence that AGEs induces cardiomyocyte autophagy by, at least in part, inhibiting the PI3K/Akt/mTOR pathway via RAGE. Previous studies showed that the accumulation of advanced glycation end products (AGEs) induce cardiomyocyte apoptoisis, leading to heart dysfunction. However, the effect of AGEs on another cell death pathway, autophagy, in cardiomyocytes remains unknown. |
format | Online Article Text |
id | pubmed-3998738 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-39987382014-04-25 Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway Hou, Xuwei Hu, Zhaohui Xu, Hanying Xu, Jian Zhang, Shunrong Zhong, Yigang He, Xiuying Wang, Ningfu Cardiovasc Diabetol Original Investigation METHODS: Rat neonate cardiomyocytes were cultured and treated with AGEs at different concentration. Two classic autophagy markers, microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1, were detected by western blot assay. The inhibition of RAGE and phosphatidylinositol 3-phosphate kinase (PI3K)/Akt/mTOR pathway were applied to cells, respectively. RESULTS: AGEs administration enhanced the expression of Beclin-1 and LC3 II in cardiomyocytes, increased the number of autophagic vacuoles and impaired the cell viability in dose-dependant manners. Also, AGEs inhibited the PI3K/Akt/mTOR pathway via RAGE. Inhibition of RAGE with RAGE antibody reduced expression of Beclin-1 and LC3 II/I and inhibited the cellular autophagy, accompanied by the reactivation of PI3K/Akt/mTOR pathway in cultured cells. Notably, the presence of inhibition of PI3K/Akt/mTOR pathway abolished the protective effect of RAGE inhibition on cardiomyocytes. CONCLUSION: This study provides evidence that AGEs induces cardiomyocyte autophagy by, at least in part, inhibiting the PI3K/Akt/mTOR pathway via RAGE. Previous studies showed that the accumulation of advanced glycation end products (AGEs) induce cardiomyocyte apoptoisis, leading to heart dysfunction. However, the effect of AGEs on another cell death pathway, autophagy, in cardiomyocytes remains unknown. BioMed Central 2014-04-14 /pmc/articles/PMC3998738/ /pubmed/24725502 http://dx.doi.org/10.1186/1475-2840-13-78 Text en Copyright © 2014 Hou et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Original Investigation Hou, Xuwei Hu, Zhaohui Xu, Hanying Xu, Jian Zhang, Shunrong Zhong, Yigang He, Xiuying Wang, Ningfu Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway |
title | Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway |
title_full | Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway |
title_fullStr | Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway |
title_full_unstemmed | Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway |
title_short | Advanced glycation endproducts trigger autophagy in cadiomyocyte Via RAGE/PI3K/AKT/mTOR pathway |
title_sort | advanced glycation endproducts trigger autophagy in cadiomyocyte via rage/pi3k/akt/mtor pathway |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998738/ https://www.ncbi.nlm.nih.gov/pubmed/24725502 http://dx.doi.org/10.1186/1475-2840-13-78 |
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