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PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity
Protein kinase C δ (PKCδ) plays an important role in nonalcoholic fatty liver disease (NAFLD), however, the mechanism remains unknown. The present study explored the role of PKCδ in NAFLD development and investigated the relationships between PKCδ, calcium homeostasis, and endoplasmic reticulum (ER)...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700272/ https://www.ncbi.nlm.nih.gov/pubmed/29046367 http://dx.doi.org/10.1042/BSR20170869 |
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author | Lai, Shujie Li, Yan Kuang, Yi Cui, Hongli Yang, Yang Sun, Wenjing Liu, Kaijun Chen, Dongfeng Yan, Qixian Wen, Liangzhi |
author_facet | Lai, Shujie Li, Yan Kuang, Yi Cui, Hongli Yang, Yang Sun, Wenjing Liu, Kaijun Chen, Dongfeng Yan, Qixian Wen, Liangzhi |
author_sort | Lai, Shujie |
collection | PubMed |
description | Protein kinase C δ (PKCδ) plays an important role in nonalcoholic fatty liver disease (NAFLD), however, the mechanism remains unknown. The present study explored the role of PKCδ in NAFLD development and investigated the relationships between PKCδ, calcium homeostasis, and endoplasmic reticulum (ER) stress (ERS). Hepatic steatosis cell model was induced by palmitic acid (PA) in L02 cells. Lipid accretion was evaluated using Oil Red O staining and a triglyceride (TG) detection kit. PKCδ was down-regulated by siRNA. RT-PCR and Western blotting were used to detect the expression of ERS markers. The fluorescence of Ca(2+) influx was recorded using confocal microscopy. Sarco-ER Ca(2+)-ATPase (SERCA) activity was measured by ultramicro-ATP enzyme test kit. PA treatment induced lipid accretion in L02 cells, destroyed the ER structure, and increased PKCδ activation in a time-dependent manner. Further, PA treatment significantly increased the expression of ERS markers, Ig heavy chain binding protein (Bip), and homologous proteins of CCAAT-enhancer binding proteins (CHOP). PKCδ silencing down-regulated Bip and CHOP expression, indicating a successful alleviation of ERS. The increased calcium storage induced by PA stimulation was significantly decreased in L02 cells treated with PKCδ siRNA compared with the negative control. Moreover, diminished SERCA activity caused by PA was recovered in PKCδ siRNA transfected cells. To the best of our knowledge, this is the first report demonstrating that the inhibition of PKCδ alleviates ERS by enhancing SERCA activity and stabilizing calcium homeostasis. |
format | Online Article Text |
id | pubmed-5700272 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57002722017-11-27 PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity Lai, Shujie Li, Yan Kuang, Yi Cui, Hongli Yang, Yang Sun, Wenjing Liu, Kaijun Chen, Dongfeng Yan, Qixian Wen, Liangzhi Biosci Rep Research Articles Protein kinase C δ (PKCδ) plays an important role in nonalcoholic fatty liver disease (NAFLD), however, the mechanism remains unknown. The present study explored the role of PKCδ in NAFLD development and investigated the relationships between PKCδ, calcium homeostasis, and endoplasmic reticulum (ER) stress (ERS). Hepatic steatosis cell model was induced by palmitic acid (PA) in L02 cells. Lipid accretion was evaluated using Oil Red O staining and a triglyceride (TG) detection kit. PKCδ was down-regulated by siRNA. RT-PCR and Western blotting were used to detect the expression of ERS markers. The fluorescence of Ca(2+) influx was recorded using confocal microscopy. Sarco-ER Ca(2+)-ATPase (SERCA) activity was measured by ultramicro-ATP enzyme test kit. PA treatment induced lipid accretion in L02 cells, destroyed the ER structure, and increased PKCδ activation in a time-dependent manner. Further, PA treatment significantly increased the expression of ERS markers, Ig heavy chain binding protein (Bip), and homologous proteins of CCAAT-enhancer binding proteins (CHOP). PKCδ silencing down-regulated Bip and CHOP expression, indicating a successful alleviation of ERS. The increased calcium storage induced by PA stimulation was significantly decreased in L02 cells treated with PKCδ siRNA compared with the negative control. Moreover, diminished SERCA activity caused by PA was recovered in PKCδ siRNA transfected cells. To the best of our knowledge, this is the first report demonstrating that the inhibition of PKCδ alleviates ERS by enhancing SERCA activity and stabilizing calcium homeostasis. Portland Press Ltd. 2017-11-23 /pmc/articles/PMC5700272/ /pubmed/29046367 http://dx.doi.org/10.1042/BSR20170869 Text en © 2017 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Articles Lai, Shujie Li, Yan Kuang, Yi Cui, Hongli Yang, Yang Sun, Wenjing Liu, Kaijun Chen, Dongfeng Yan, Qixian Wen, Liangzhi PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity |
title | PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity |
title_full | PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity |
title_fullStr | PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity |
title_full_unstemmed | PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity |
title_short | PKCδ silencing alleviates saturated fatty acid induced ER stress by enhancing SERCA activity |
title_sort | pkcδ silencing alleviates saturated fatty acid induced er stress by enhancing serca activity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5700272/ https://www.ncbi.nlm.nih.gov/pubmed/29046367 http://dx.doi.org/10.1042/BSR20170869 |
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