Berberine alleviates palmitic acid‑induced podocyte apoptosis by reducing reactive oxygen species‑mediated endoplasmic reticulum stress
Lipid accumulation in podocytes can lead to the destruction of cellular morphology, in addition to cell dysfunction and apoptosis, which is a key factor in the progression of chronic kidney disease (CKD). Berberine (BBR) is an isoquinoline alkaloid extracted from medicinal plants such as Coptis chin...
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description | Lipid accumulation in podocytes can lead to the destruction of cellular morphology, in addition to cell dysfunction and apoptosis, which is a key factor in the progression of chronic kidney disease (CKD). Berberine (BBR) is an isoquinoline alkaloid extracted from medicinal plants such as Coptis chinensis, which has been reported to have a lipid‑lowering effect and prevent CKD progression. Therefore, the present study aimed to investigate the effect of BBR on palmitic acid (PA)‑induced podocyte apoptosis and its specific mechanism using an in vitro model. Cell death was measured using the Cell Counting Kit‑8 colorimetric assay. Cell apoptotic rate was assessed by flow cytometry. The expression of endoplasmic reticulum (ER) stress‑ and apoptosis‑related proteins was detected by western blotting or immunofluorescence. Reactive oxygen species (ROS) were evaluated by 2',7'‑dichlorofluorescein diacetate fluorescence staining. The results of the present study revealed that BBR treatment decreased PA‑induced podocyte apoptosis. In addition, 4‑phenylbutyric acid significantly reduced PA‑induced cell apoptosis and the expression of ER stress‑related proteins, which indicated that ER stress was involved in PA‑induced podocyte apoptosis. In addition, N‑acetylcysteine inhibited PA‑induced excessive ROS production, ER stress and cell apoptosis of podocytes. BBR also significantly reduced PA‑induced ROS production and ER stress in podocytes. These results suggested that PA mediated podocyte apoptosis through enhancing ER stress and the production of ROS. In conclusion, BBR may protect against PA‑induced podocyte apoptosis, and suppression of ROS‑dependent ER stress may be the key mechanism underlying the protective effects of BBR. |
doi_str_mv | 10.3892/mmr.2020.11641 |
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fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7673344</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A647367487</galeid><sourcerecordid>A647367487</sourcerecordid><originalsourceid>FETCH-LOGICAL-c485t-6d219ba8df9c29763d119beab312db104608a68acd249f20963aeb5ba3f744bf3</originalsourceid><addsrcrecordid>eNptkj1vFDEQhi0EIiHQUiJL1Hf4a712gxQiAkiR0oTa8tqzh6Nde7F3T7mOnoq_mF-CjxwhSJELz3jeeTy2XoReU7LmSrN345jXjDCyplQK-gQd01bTFSdEPD3ETOv2CL0o5ZoQ2bBGP0dHnNcS0eoY_fwAuYMcImA7DLANdoaCJzuMYQ4OWxf87Y9fIfrFgcdT8snt5qqd0jSnEgrudjhDrYa4qYF1c9gCTje7DURcJnABSgWM4PdkjyH6NA22jBWeoV6xDMuIy5yhlJfoWW-HAq8O-wn6ev7x6uzz6uLy05ez04uVE6qZV9IzqjurfK8d063kntYcbMcp8x0lQhJlpbLOM6F7RrTkFrqms7xvheh6foLe33GnpauDOYhztoOZchht3plkg_m_EsM3s0lb08qWcyEq4O0BkNP3BcpsrtOSY53ZMCGVVKxh8p9qYwcwIfapwtwYijOnUrRctkK1VbV-RFWXh_pHKUIf6vljDS6nUjL094NTYvaeMNUTZu8J88cTteHNw-fey_-agP8GIaa4qQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2468682526</pqid></control><display><type>article</type><title>Berberine alleviates palmitic acid‑induced podocyte apoptosis by reducing reactive oxygen species‑mediated endoplasmic reticulum stress</title><source>Spandidos Publications Journals</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Xiang, Xing-Yang ; Liu, Ting ; Wu, Yue ; Jiang, Xu-Shun ; He, Jun-Ling ; Chen, Xue-Mei ; Du, Xiao-Gang</creator><creatorcontrib>Xiang, Xing-Yang ; Liu, Ting ; Wu, Yue ; Jiang, Xu-Shun ; He, Jun-Ling ; Chen, Xue-Mei ; Du, Xiao-Gang</creatorcontrib><description>Lipid accumulation in podocytes can lead to the destruction of cellular morphology, in addition to cell dysfunction and apoptosis, which is a key factor in the progression of chronic kidney disease (CKD). Berberine (BBR) is an isoquinoline alkaloid extracted from medicinal plants such as Coptis chinensis, which has been reported to have a lipid‑lowering effect and prevent CKD progression. Therefore, the present study aimed to investigate the effect of BBR on palmitic acid (PA)‑induced podocyte apoptosis and its specific mechanism using an in vitro model. Cell death was measured using the Cell Counting Kit‑8 colorimetric assay. Cell apoptotic rate was assessed by flow cytometry. The expression of endoplasmic reticulum (ER) stress‑ and apoptosis‑related proteins was detected by western blotting or immunofluorescence. Reactive oxygen species (ROS) were evaluated by 2',7'‑dichlorofluorescein diacetate fluorescence staining. The results of the present study revealed that BBR treatment decreased PA‑induced podocyte apoptosis. In addition, 4‑phenylbutyric acid significantly reduced PA‑induced cell apoptosis and the expression of ER stress‑related proteins, which indicated that ER stress was involved in PA‑induced podocyte apoptosis. In addition, N‑acetylcysteine inhibited PA‑induced excessive ROS production, ER stress and cell apoptosis of podocytes. BBR also significantly reduced PA‑induced ROS production and ER stress in podocytes. These results suggested that PA mediated podocyte apoptosis through enhancing ER stress and the production of ROS. In conclusion, BBR may protect against PA‑induced podocyte apoptosis, and suppression of ROS‑dependent ER stress may be the key mechanism underlying the protective effects of BBR.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2020.11641</identifier><identifier>PMID: 33179098</identifier><language>eng</language><publisher>Greece: Spandidos Publications</publisher><subject>Acetylcysteine ; Animals ; Apoptosis ; Apoptosis - drug effects ; Berberine ; Berberine - pharmacology ; Biotechnology ; Care and treatment ; Cell death ; Cell Line ; Colorimetry ; Cytology ; Development and progression ; Endoplasmic reticulum ; Endoplasmic Reticulum Stress - drug effects ; Flow cytometry ; Gene Expression Regulation - drug effects ; Gene Regulatory Networks - drug effects ; Health aspects ; Immunofluorescence ; Kidney diseases ; Kinases ; Lipids ; Medicinal plants ; Mice ; Oxidative stress ; Oxidative Stress - drug effects ; Palmitic acid ; Palmitic Acid - adverse effects ; Phenylbutyric acid ; Podocytes - cytology ; Podocytes - drug effects ; Podocytes - metabolism ; Proteins ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Western blotting</subject><ispartof>Molecular medicine reports, 2021-01, Vol.23 (1), p.1-1</ispartof><rights>COPYRIGHT 2021 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2021</rights><rights>Copyright: © Xiang et al. 2020</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c485t-6d219ba8df9c29763d119beab312db104608a68acd249f20963aeb5ba3f744bf3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33179098$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiang, Xing-Yang</creatorcontrib><creatorcontrib>Liu, Ting</creatorcontrib><creatorcontrib>Wu, Yue</creatorcontrib><creatorcontrib>Jiang, Xu-Shun</creatorcontrib><creatorcontrib>He, Jun-Ling</creatorcontrib><creatorcontrib>Chen, Xue-Mei</creatorcontrib><creatorcontrib>Du, Xiao-Gang</creatorcontrib><title>Berberine alleviates palmitic acid‑induced podocyte apoptosis by reducing reactive oxygen species‑mediated endoplasmic reticulum stress</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>Lipid accumulation in podocytes can lead to the destruction of cellular morphology, in addition to cell dysfunction and apoptosis, which is a key factor in the progression of chronic kidney disease (CKD). Berberine (BBR) is an isoquinoline alkaloid extracted from medicinal plants such as Coptis chinensis, which has been reported to have a lipid‑lowering effect and prevent CKD progression. Therefore, the present study aimed to investigate the effect of BBR on palmitic acid (PA)‑induced podocyte apoptosis and its specific mechanism using an in vitro model. Cell death was measured using the Cell Counting Kit‑8 colorimetric assay. Cell apoptotic rate was assessed by flow cytometry. The expression of endoplasmic reticulum (ER) stress‑ and apoptosis‑related proteins was detected by western blotting or immunofluorescence. Reactive oxygen species (ROS) were evaluated by 2',7'‑dichlorofluorescein diacetate fluorescence staining. The results of the present study revealed that BBR treatment decreased PA‑induced podocyte apoptosis. In addition, 4‑phenylbutyric acid significantly reduced PA‑induced cell apoptosis and the expression of ER stress‑related proteins, which indicated that ER stress was involved in PA‑induced podocyte apoptosis. In addition, N‑acetylcysteine inhibited PA‑induced excessive ROS production, ER stress and cell apoptosis of podocytes. BBR also significantly reduced PA‑induced ROS production and ER stress in podocytes. These results suggested that PA mediated podocyte apoptosis through enhancing ER stress and the production of ROS. In conclusion, BBR may protect against PA‑induced podocyte apoptosis, and suppression of ROS‑dependent ER stress may be the key mechanism underlying the protective effects of BBR.</description><subject>Acetylcysteine</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Berberine</subject><subject>Berberine - pharmacology</subject><subject>Biotechnology</subject><subject>Care and treatment</subject><subject>Cell death</subject><subject>Cell Line</subject><subject>Colorimetry</subject><subject>Cytology</subject><subject>Development and progression</subject><subject>Endoplasmic reticulum</subject><subject>Endoplasmic Reticulum Stress - drug effects</subject><subject>Flow cytometry</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Gene Regulatory Networks - drug effects</subject><subject>Health aspects</subject><subject>Immunofluorescence</subject><subject>Kidney diseases</subject><subject>Kinases</subject><subject>Lipids</subject><subject>Medicinal plants</subject><subject>Mice</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Palmitic acid</subject><subject>Palmitic Acid - adverse effects</subject><subject>Phenylbutyric acid</subject><subject>Podocytes - cytology</subject><subject>Podocytes - drug effects</subject><subject>Podocytes - metabolism</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Western blotting</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkj1vFDEQhi0EIiHQUiJL1Hf4a712gxQiAkiR0oTa8tqzh6Nde7F3T7mOnoq_mF-CjxwhSJELz3jeeTy2XoReU7LmSrN345jXjDCyplQK-gQd01bTFSdEPD3ETOv2CL0o5ZoQ2bBGP0dHnNcS0eoY_fwAuYMcImA7DLANdoaCJzuMYQ4OWxf87Y9fIfrFgcdT8snt5qqd0jSnEgrudjhDrYa4qYF1c9gCTje7DURcJnABSgWM4PdkjyH6NA22jBWeoV6xDMuIy5yhlJfoWW-HAq8O-wn6ev7x6uzz6uLy05ez04uVE6qZV9IzqjurfK8d063kntYcbMcp8x0lQhJlpbLOM6F7RrTkFrqms7xvheh6foLe33GnpauDOYhztoOZchht3plkg_m_EsM3s0lb08qWcyEq4O0BkNP3BcpsrtOSY53ZMCGVVKxh8p9qYwcwIfapwtwYijOnUrRctkK1VbV-RFWXh_pHKUIf6vljDS6nUjL094NTYvaeMNUTZu8J88cTteHNw-fey_-agP8GIaa4qQ</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Xiang, Xing-Yang</creator><creator>Liu, Ting</creator><creator>Wu, Yue</creator><creator>Jiang, Xu-Shun</creator><creator>He, Jun-Ling</creator><creator>Chen, Xue-Mei</creator><creator>Du, Xiao-Gang</creator><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><general>D.A. Spandidos</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20210101</creationdate><title>Berberine alleviates palmitic acid‑induced podocyte apoptosis by reducing reactive oxygen species‑mediated endoplasmic reticulum stress</title><author>Xiang, Xing-Yang ; Liu, Ting ; Wu, Yue ; Jiang, Xu-Shun ; He, Jun-Ling ; Chen, Xue-Mei ; Du, Xiao-Gang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c485t-6d219ba8df9c29763d119beab312db104608a68acd249f20963aeb5ba3f744bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetylcysteine</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Berberine</topic><topic>Berberine - pharmacology</topic><topic>Biotechnology</topic><topic>Care and treatment</topic><topic>Cell death</topic><topic>Cell Line</topic><topic>Colorimetry</topic><topic>Cytology</topic><topic>Development and progression</topic><topic>Endoplasmic reticulum</topic><topic>Endoplasmic Reticulum Stress - drug effects</topic><topic>Flow cytometry</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Regulatory Networks - drug effects</topic><topic>Health aspects</topic><topic>Immunofluorescence</topic><topic>Kidney diseases</topic><topic>Kinases</topic><topic>Lipids</topic><topic>Medicinal plants</topic><topic>Mice</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Palmitic acid</topic><topic>Palmitic Acid - adverse effects</topic><topic>Phenylbutyric acid</topic><topic>Podocytes - cytology</topic><topic>Podocytes - drug effects</topic><topic>Podocytes - metabolism</topic><topic>Proteins</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Western blotting</topic><toplevel>online_resources</toplevel><creatorcontrib>Xiang, Xing-Yang</creatorcontrib><creatorcontrib>Liu, Ting</creatorcontrib><creatorcontrib>Wu, Yue</creatorcontrib><creatorcontrib>Jiang, Xu-Shun</creatorcontrib><creatorcontrib>He, Jun-Ling</creatorcontrib><creatorcontrib>Chen, Xue-Mei</creatorcontrib><creatorcontrib>Du, Xiao-Gang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular medicine reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiang, Xing-Yang</au><au>Liu, Ting</au><au>Wu, Yue</au><au>Jiang, Xu-Shun</au><au>He, Jun-Ling</au><au>Chen, Xue-Mei</au><au>Du, Xiao-Gang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Berberine alleviates palmitic acid‑induced podocyte apoptosis by reducing reactive oxygen species‑mediated endoplasmic reticulum stress</atitle><jtitle>Molecular medicine reports</jtitle><addtitle>Mol Med Rep</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>23</volume><issue>1</issue><spage>1</spage><epage>1</epage><pages>1-1</pages><issn>1791-2997</issn><eissn>1791-3004</eissn><abstract>Lipid accumulation in podocytes can lead to the destruction of cellular morphology, in addition to cell dysfunction and apoptosis, which is a key factor in the progression of chronic kidney disease (CKD). Berberine (BBR) is an isoquinoline alkaloid extracted from medicinal plants such as Coptis chinensis, which has been reported to have a lipid‑lowering effect and prevent CKD progression. Therefore, the present study aimed to investigate the effect of BBR on palmitic acid (PA)‑induced podocyte apoptosis and its specific mechanism using an in vitro model. Cell death was measured using the Cell Counting Kit‑8 colorimetric assay. Cell apoptotic rate was assessed by flow cytometry. The expression of endoplasmic reticulum (ER) stress‑ and apoptosis‑related proteins was detected by western blotting or immunofluorescence. Reactive oxygen species (ROS) were evaluated by 2',7'‑dichlorofluorescein diacetate fluorescence staining. The results of the present study revealed that BBR treatment decreased PA‑induced podocyte apoptosis. In addition, 4‑phenylbutyric acid significantly reduced PA‑induced cell apoptosis and the expression of ER stress‑related proteins, which indicated that ER stress was involved in PA‑induced podocyte apoptosis. In addition, N‑acetylcysteine inhibited PA‑induced excessive ROS production, ER stress and cell apoptosis of podocytes. BBR also significantly reduced PA‑induced ROS production and ER stress in podocytes. These results suggested that PA mediated podocyte apoptosis through enhancing ER stress and the production of ROS. In conclusion, BBR may protect against PA‑induced podocyte apoptosis, and suppression of ROS‑dependent ER stress may be the key mechanism underlying the protective effects of BBR.</abstract><cop>Greece</cop><pub>Spandidos Publications</pub><pmid>33179098</pmid><doi>10.3892/mmr.2020.11641</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Acetylcysteine Animals Apoptosis Apoptosis - drug effects Berberine Berberine - pharmacology Biotechnology Care and treatment Cell death Cell Line Colorimetry Cytology Development and progression Endoplasmic reticulum Endoplasmic Reticulum Stress - drug effects Flow cytometry Gene Expression Regulation - drug effects Gene Regulatory Networks - drug effects Health aspects Immunofluorescence Kidney diseases Kinases Lipids Medicinal plants Mice Oxidative stress Oxidative Stress - drug effects Palmitic acid Palmitic Acid - adverse effects Phenylbutyric acid Podocytes - cytology Podocytes - drug effects Podocytes - metabolism Proteins Reactive oxygen species Reactive Oxygen Species - metabolism Western blotting |
title | Berberine alleviates palmitic acid‑induced podocyte apoptosis by reducing reactive oxygen species‑mediated endoplasmic reticulum stress |
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