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Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing K(ATP) channel
BACKGROUND: Sulfonylureas (SUs) are widely prescribed for the treatment of type 2 diabetes (T2DM). Sulfonylurea receptors (SURs) are their main functional receptors. These receptors are also found in kidney, especially the tubular cells. However, the effects of SUs on renal proximal tubular epitheli...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122448/ https://www.ncbi.nlm.nih.gov/pubmed/30180807 http://dx.doi.org/10.1186/s10020-018-0042-5 |
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author | Zhang, Rui Zhou, Xiaojun Shen, Xue Xie, Tianyue Xu, Chunmei Zou, Zhiwei Dong, Jianjun Liao, Lin |
author_facet | Zhang, Rui Zhou, Xiaojun Shen, Xue Xie, Tianyue Xu, Chunmei Zou, Zhiwei Dong, Jianjun Liao, Lin |
author_sort | Zhang, Rui |
collection | PubMed |
description | BACKGROUND: Sulfonylureas (SUs) are widely prescribed for the treatment of type 2 diabetes (T2DM). Sulfonylurea receptors (SURs) are their main functional receptors. These receptors are also found in kidney, especially the tubular cells. However, the effects of SUs on renal proximal tubular epithelial cells (PTECs) were unclear. METHODS: Three commonly used SUs were included in this study to investigate if different SUs have different effects on the apoptosis of PTECs. HK-2 cells were exposed to SUs for 24 h prior to exposure to 30 mM glucose, the apoptosis rate was evaluated by Annexin/PI flow cytometry. Bcl-2, Bax and the ratio of LC3II to LC3I were also studied by western blot in vitro. Diazoxide was used to evaluate the role of K(ATP) channel in SUs-induced apoptosis of PTECs. A Student’s t-test was used to assess significance for data within two groups. RESULTS: Treatment with glibenclamide aggravated the apoptosis of HK-2 cells in high-glucose, as indicated by a significant decrease in the expression of Bcl-2 and increase in Bax. Additionally, the decreased LC3II/LC3I reflects that the autophagy was inhibited by glibenclamide. Similar but less pronounced change was found in glimepiride group, however, nearly opposite effects were found in gliclazide group. Further, the effects of glibenclamide on apoptosis promotion and the decreased LC3II/LC3I were ameliorated obviously by treatment with 100uM diazoxide. The potential protection effect of gliclazide was also inhibited after opening the K(ATP) channel. CONCLUSION: Our results suggest that, the effects of glibenclamide and glimepiride on PTECs apoptosis, especially the former, were achieved in part by closing the K(ATP) channel. In contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide showed an inhibitory effect on apoptosis of PTECs, which may have a benefit in the preservation of functional PTECs mass. |
format | Online Article Text |
id | pubmed-6122448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-61224482018-09-06 Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing K(ATP) channel Zhang, Rui Zhou, Xiaojun Shen, Xue Xie, Tianyue Xu, Chunmei Zou, Zhiwei Dong, Jianjun Liao, Lin Mol Med Research Article BACKGROUND: Sulfonylureas (SUs) are widely prescribed for the treatment of type 2 diabetes (T2DM). Sulfonylurea receptors (SURs) are their main functional receptors. These receptors are also found in kidney, especially the tubular cells. However, the effects of SUs on renal proximal tubular epithelial cells (PTECs) were unclear. METHODS: Three commonly used SUs were included in this study to investigate if different SUs have different effects on the apoptosis of PTECs. HK-2 cells were exposed to SUs for 24 h prior to exposure to 30 mM glucose, the apoptosis rate was evaluated by Annexin/PI flow cytometry. Bcl-2, Bax and the ratio of LC3II to LC3I were also studied by western blot in vitro. Diazoxide was used to evaluate the role of K(ATP) channel in SUs-induced apoptosis of PTECs. A Student’s t-test was used to assess significance for data within two groups. RESULTS: Treatment with glibenclamide aggravated the apoptosis of HK-2 cells in high-glucose, as indicated by a significant decrease in the expression of Bcl-2 and increase in Bax. Additionally, the decreased LC3II/LC3I reflects that the autophagy was inhibited by glibenclamide. Similar but less pronounced change was found in glimepiride group, however, nearly opposite effects were found in gliclazide group. Further, the effects of glibenclamide on apoptosis promotion and the decreased LC3II/LC3I were ameliorated obviously by treatment with 100uM diazoxide. The potential protection effect of gliclazide was also inhibited after opening the K(ATP) channel. CONCLUSION: Our results suggest that, the effects of glibenclamide and glimepiride on PTECs apoptosis, especially the former, were achieved in part by closing the K(ATP) channel. In contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide showed an inhibitory effect on apoptosis of PTECs, which may have a benefit in the preservation of functional PTECs mass. BioMed Central 2018-09-04 /pmc/articles/PMC6122448/ /pubmed/30180807 http://dx.doi.org/10.1186/s10020-018-0042-5 Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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 | Research Article Zhang, Rui Zhou, Xiaojun Shen, Xue Xie, Tianyue Xu, Chunmei Zou, Zhiwei Dong, Jianjun Liao, Lin Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing K(ATP) channel |
title | Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing K(ATP) channel |
title_full | Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing K(ATP) channel |
title_fullStr | Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing K(ATP) channel |
title_full_unstemmed | Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing K(ATP) channel |
title_short | Different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing K(ATP) channel |
title_sort | different sulfonylureas induce the apoptosis of proximal tubular epithelial cell differently via closing k(atp) channel |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122448/ https://www.ncbi.nlm.nih.gov/pubmed/30180807 http://dx.doi.org/10.1186/s10020-018-0042-5 |
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