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Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes
Loss of podocytes is a hallmark of diabetic nephropathy, and a growing body of evidence indicates that podocytes are susceptible to palmitic acid (PA). We have previously shown that AS-IV inhibited PA-induced podocyte apoptosis by activating sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), which in...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925475/ https://www.ncbi.nlm.nih.gov/pubmed/33606151 http://dx.doi.org/10.1007/s11033-021-06204-4 |
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author | Zang, Yingjun Liu, Shuang Cao, Aili Shan, Xiangyu Deng, Wenjuan Li, Zhijun Wang, Hao Wang, Yunman Wang, Li Peng, Wen |
author_facet | Zang, Yingjun Liu, Shuang Cao, Aili Shan, Xiangyu Deng, Wenjuan Li, Zhijun Wang, Hao Wang, Yunman Wang, Li Peng, Wen |
author_sort | Zang, Yingjun |
collection | PubMed |
description | Loss of podocytes is a hallmark of diabetic nephropathy, and a growing body of evidence indicates that podocytes are susceptible to palmitic acid (PA). We have previously shown that AS-IV inhibited PA-induced podocyte apoptosis by activating sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), which indicate calcium regulation may involve in the process. Immunofluorescence staining, Western blot and flow cytometry were used to measure the protective efficacy of AS-IV to ameliorate PA-induced ER stress and podocyte apoptosis. Meanwhile, AS-IV inhibited cytochrome c release, decreased mitochondrial membrane potential, accompany with the depletion of endoplasmic reticulum Ca(2+) and elevation of cytosolic and mitochondrial Ca(2+). Sequestration of cytosolic calcium with BAPTA-AM limited the response of podocyte apoptosis, while during the process the effect of AS-IV was also restrained. In contrast, elevation of cytosolic calcium with calcium ionophore ionomycin was depressed by AS-IV addition. Furthermore, inhibiting TRPC6 expression with SKF96365 or TRPC6 siRNA counteracted the beneficial effect of AS-IV. Our study provides further evidence to conclude the inhibitory effect of AS-IV to podocyte apoptosis is Ca(2+)-dependent. And the efficacy correlates with inhibiting TRPC6-mediated Ca(2+) influx, and then cellular Ca(2+) disturbance was coordinated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11033-021-06204-4. |
format | Online Article Text |
id | pubmed-7925475 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-79254752021-03-19 Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes Zang, Yingjun Liu, Shuang Cao, Aili Shan, Xiangyu Deng, Wenjuan Li, Zhijun Wang, Hao Wang, Yunman Wang, Li Peng, Wen Mol Biol Rep Original Article Loss of podocytes is a hallmark of diabetic nephropathy, and a growing body of evidence indicates that podocytes are susceptible to palmitic acid (PA). We have previously shown that AS-IV inhibited PA-induced podocyte apoptosis by activating sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA), which indicate calcium regulation may involve in the process. Immunofluorescence staining, Western blot and flow cytometry were used to measure the protective efficacy of AS-IV to ameliorate PA-induced ER stress and podocyte apoptosis. Meanwhile, AS-IV inhibited cytochrome c release, decreased mitochondrial membrane potential, accompany with the depletion of endoplasmic reticulum Ca(2+) and elevation of cytosolic and mitochondrial Ca(2+). Sequestration of cytosolic calcium with BAPTA-AM limited the response of podocyte apoptosis, while during the process the effect of AS-IV was also restrained. In contrast, elevation of cytosolic calcium with calcium ionophore ionomycin was depressed by AS-IV addition. Furthermore, inhibiting TRPC6 expression with SKF96365 or TRPC6 siRNA counteracted the beneficial effect of AS-IV. Our study provides further evidence to conclude the inhibitory effect of AS-IV to podocyte apoptosis is Ca(2+)-dependent. And the efficacy correlates with inhibiting TRPC6-mediated Ca(2+) influx, and then cellular Ca(2+) disturbance was coordinated. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11033-021-06204-4. Springer Netherlands 2021-02-19 2021 /pmc/articles/PMC7925475/ /pubmed/33606151 http://dx.doi.org/10.1007/s11033-021-06204-4 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Original Article Zang, Yingjun Liu, Shuang Cao, Aili Shan, Xiangyu Deng, Wenjuan Li, Zhijun Wang, Hao Wang, Yunman Wang, Li Peng, Wen Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes |
title | Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes |
title_full | Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes |
title_fullStr | Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes |
title_full_unstemmed | Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes |
title_short | Astragaloside IV inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes |
title_sort | astragaloside iv inhibits palmitic acid-induced apoptosis through regulation of calcium homeostasis in mice podocytes |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925475/ https://www.ncbi.nlm.nih.gov/pubmed/33606151 http://dx.doi.org/10.1007/s11033-021-06204-4 |
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