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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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2014/658589 |
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| author | Chuan Lv Can Wu Yue-hong Zhou Ying Shao Guan Wang Qiu-yue Wang |
| author_facet | Chuan Lv Can Wu Yue-hong Zhou Ying Shao Guan Wang Qiu-yue Wang |
| author_sort | Chuan Lv |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-724a960349654e7c8e9dfc1f08bf75de |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-724a960349654e7c8e9dfc1f08bf75de2025-02-03T01:31:33ZengWileyInternational Journal of Endocrinology1687-83371687-83452014-01-01201410.1155/2014/658589658589Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 PathwayChuan Lv0Can Wu1Yue-hong Zhou2Ying Shao3Guan Wang4Qiu-yue Wang5Division of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, ChinaDivision of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, ChinaDivision of Endocrinology, Shenyang No. 8 Hospital, Shenyang, Liaoning 110024, ChinaDivision of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, ChinaClinical Medicine of Seven-Year Education, China Medical University, Shenyang, Liaoning 110001, ChinaDivision of Endocrinology, First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, ChinaThe 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.http://dx.doi.org/10.1155/2014/658589 |
| spellingShingle | Chuan Lv Can Wu Yue-hong Zhou Ying Shao Guan Wang Qiu-yue Wang Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway International Journal of Endocrinology |
| 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 |
| url | http://dx.doi.org/10.1155/2014/658589 |
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