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Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway
The aim of this study was to investigate whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation and extracellular matrix production via mTOR/p70S6K/4E-BP1 signaling. The effect of LA on high glucose-induced cell proliferation, fibronectin (FN), and collagen type I...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229972/ https://www.ncbi.nlm.nih.gov/pubmed/25530759 http://dx.doi.org/10.1155/2014/658589 |
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author | Lv, Chuan Wu, Can Zhou, Yue-hong Shao, Ying Wang, Guan Wang, Qiu-yue |
author_facet | Lv, Chuan Wu, Can Zhou, Yue-hong Shao, Ying Wang, Guan Wang, Qiu-yue |
author_sort | Lv, Chuan |
collection | PubMed |
description | The aim of this study was to investigate whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation and extracellular matrix production via mTOR/p70S6K/4E-BP1 signaling. The effect of LA on high glucose-induced cell proliferation, fibronectin (FN), and collagen type I (collagen-I) expression and its mechanisms were examined in cultured rat mesangial cells by methylthiazol tetrazolium (MTT) assay, flow cytometry, ELISA assay, and western blot, respectively. LA at a relatively low concentration (0.25 mmol/L) acted as a growth factor in rat mesangial cells, promoted entry of cell cycle into S phase, extracellular matrix formation, and phosphorylated AKT, mTOR, p70S6K, and 4E-BP1. These effects disappeared when AKT expression was downregulated with PI3K/AKT inhibitor LY294002. Conversely, LA at a higher concentration (1.0 mmol/L) inhibited high glucose-induced rat mesangial cell proliferation, entry of cell cycle into S phase, and extracellular matrix exertion, as well as phosphorylation of mTOR, p70S6K, and 4E-BP1 but enhanced the activity of AMPK. However, these effects disappeared when AMPK activity was inhibited with CaMKK inhibitor STO-609. These results suggest that LA dose-dependently regulates mesangial cell proliferation and matrix protein secretion by mTOR/p70S6K/4E-BP1 signaling pathway under high glucose conditions. |
format | Online Article Text |
id | pubmed-4229972 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-42299722014-12-21 Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway Lv, Chuan Wu, Can Zhou, Yue-hong Shao, Ying Wang, Guan Wang, Qiu-yue Int J Endocrinol Research Article The aim of this study was to investigate whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation and extracellular matrix production via mTOR/p70S6K/4E-BP1 signaling. The effect of LA on high glucose-induced cell proliferation, fibronectin (FN), and collagen type I (collagen-I) expression and its mechanisms were examined in cultured rat mesangial cells by methylthiazol tetrazolium (MTT) assay, flow cytometry, ELISA assay, and western blot, respectively. LA at a relatively low concentration (0.25 mmol/L) acted as a growth factor in rat mesangial cells, promoted entry of cell cycle into S phase, extracellular matrix formation, and phosphorylated AKT, mTOR, p70S6K, and 4E-BP1. These effects disappeared when AKT expression was downregulated with PI3K/AKT inhibitor LY294002. Conversely, LA at a higher concentration (1.0 mmol/L) inhibited high glucose-induced rat mesangial cell proliferation, entry of cell cycle into S phase, and extracellular matrix exertion, as well as phosphorylation of mTOR, p70S6K, and 4E-BP1 but enhanced the activity of AMPK. However, these effects disappeared when AMPK activity was inhibited with CaMKK inhibitor STO-609. These results suggest that LA dose-dependently regulates mesangial cell proliferation and matrix protein secretion by mTOR/p70S6K/4E-BP1 signaling pathway under high glucose conditions. Hindawi Publishing Corporation 2014 2014-10-30 /pmc/articles/PMC4229972/ /pubmed/25530759 http://dx.doi.org/10.1155/2014/658589 Text en Copyright © 2014 Chuan Lv et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Lv, Chuan Wu, Can Zhou, Yue-hong Shao, Ying Wang, Guan Wang, Qiu-yue Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway |
title | Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway |
title_full | Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway |
title_fullStr | Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway |
title_full_unstemmed | Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway |
title_short | Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway |
title_sort | alpha lipoic acid modulated high glucose-induced rat mesangial cell dysfunction via mtor/p70s6k/4e-bp1 pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4229972/ https://www.ncbi.nlm.nih.gov/pubmed/25530759 http://dx.doi.org/10.1155/2014/658589 |
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