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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...

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Autores principales: Lv, Chuan, Wu, Can, Zhou, Yue-hong, Shao, Ying, Wang, Guan, Wang, Qiu-yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
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.
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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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