Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway
Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca is required for mitochondrial ATP...
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| Veröffentlicht in: | International journal of molecular sciences 2019-03, Vol.20 (7), p.1570 |
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| description | Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca
is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney. |
| doi_str_mv | 10.3390/ijms20071570 |
| format | Article |
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is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20071570</identifier><identifier>PMID: 30934807</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Albumins ; AMP-activated protein kinase ; Antihypertensives ; Apoptosis ; Autophagy ; Biosynthesis ; CD36 antigen ; Cell lines ; Cholesterol ; Fatty acids ; Fibrosis ; Hepatocytes ; Hepatoma ; Kidneys ; Kinases ; Lipids ; Lipogenesis ; Liver cancer ; Metabolism ; Nifedipine ; Oxidation ; Phagocytosis ; Phosphorylation ; Proteins ; Proteinuria ; Renal insufficiency ; Sterol regulatory element-binding protein ; Sterols ; Transcription ; Translocase</subject><ispartof>International journal of molecular sciences, 2019-03, Vol.20 (7), p.1570</ispartof><rights>2019. This work is licensed under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c412t-dfb921a1709cac725a895f6c63e204d66ba9eae5200f65b7db2fc714986fc0063</citedby><cites>FETCH-LOGICAL-c412t-dfb921a1709cac725a895f6c63e204d66ba9eae5200f65b7db2fc714986fc0063</cites><orcidid>0000-0001-7861-5054 ; 0000-0002-4542-4195</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480582/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6480582/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30934807$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lin, Yen-Chung</creatorcontrib><creatorcontrib>Wu, Mai-Szu</creatorcontrib><creatorcontrib>Lin, Yuh-Feng</creatorcontrib><creatorcontrib>Chen, Chang-Rong</creatorcontrib><creatorcontrib>Chen, Chang-Yu</creatorcontrib><creatorcontrib>Chen, Chang-Jui</creatorcontrib><creatorcontrib>Shen, Che-Chou</creatorcontrib><creatorcontrib>Chen, Kuan-Chou</creatorcontrib><creatorcontrib>Peng, Chiung-Chi</creatorcontrib><title>Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca
is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.</description><subject>Albumins</subject><subject>AMP-activated protein kinase</subject><subject>Antihypertensives</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biosynthesis</subject><subject>CD36 antigen</subject><subject>Cell lines</subject><subject>Cholesterol</subject><subject>Fatty acids</subject><subject>Fibrosis</subject><subject>Hepatocytes</subject><subject>Hepatoma</subject><subject>Kidneys</subject><subject>Kinases</subject><subject>Lipids</subject><subject>Lipogenesis</subject><subject>Liver cancer</subject><subject>Metabolism</subject><subject>Nifedipine</subject><subject>Oxidation</subject><subject>Phagocytosis</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Proteinuria</subject><subject>Renal insufficiency</subject><subject>Sterol regulatory element-binding protein</subject><subject>Sterols</subject><subject>Transcription</subject><subject>Translocase</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUtLxDAURoMoPkZ3rqXgxoXVPJpmshFUfOGo42sd0vTWydBpatIq8--N-GB0dS_cw8c9fAhtE3zAmMSHdjoLFGNBuMBLaJ1klKYY52J5YV9DGyFMMaaMcrmK1hiWLBtisY7ub20FpW1tA8mNK_tadxCSB2h0nYxs616ggWBD8mZ10k0gOb4ZX6ePD2cn4-TJ6yYYb9vOuk98rLvJu55vopVK1wG2vucAPZ-fPZ1epqO7i6vT41FqMkK7tKwKSYkmAkujjaBcDyWvcpMzoDgr87zQEjTwqFblvBBlQSsjSCaHeWWiExugo6_cti9mUBpoOq9r1Xo7036unLbq76WxE_Xi3lQezfmQxoC97wDvXnsInZrZYKCudQOuD4pSTImUmZAR3f2HTl3vo3SkGKOUMyF5pPa_KONdCB6q32cIVp9dqcWuIr6zKPAL_5TDPgAbtI-2</recordid><startdate>20190329</startdate><enddate>20190329</enddate><creator>Lin, Yen-Chung</creator><creator>Wu, Mai-Szu</creator><creator>Lin, Yuh-Feng</creator><creator>Chen, Chang-Rong</creator><creator>Chen, Chang-Yu</creator><creator>Chen, Chang-Jui</creator><creator>Shen, Che-Chou</creator><creator>Chen, Kuan-Chou</creator><creator>Peng, Chiung-Chi</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PHGZM</scope><scope>PHGZT</scope><scope>PIMPY</scope><scope>PJZUB</scope><scope>PKEHL</scope><scope>PPXIY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7861-5054</orcidid><orcidid>https://orcid.org/0000-0002-4542-4195</orcidid></search><sort><creationdate>20190329</creationdate><title>Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway</title><author>Lin, Yen-Chung ; Wu, Mai-Szu ; Lin, Yuh-Feng ; Chen, Chang-Rong ; Chen, Chang-Yu ; Chen, Chang-Jui ; Shen, Che-Chou ; Chen, Kuan-Chou ; Peng, Chiung-Chi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c412t-dfb921a1709cac725a895f6c63e204d66ba9eae5200f65b7db2fc714986fc0063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Albumins</topic><topic>AMP-activated protein kinase</topic><topic>Antihypertensives</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biosynthesis</topic><topic>CD36 antigen</topic><topic>Cell lines</topic><topic>Cholesterol</topic><topic>Fatty acids</topic><topic>Fibrosis</topic><topic>Hepatocytes</topic><topic>Hepatoma</topic><topic>Kidneys</topic><topic>Kinases</topic><topic>Lipids</topic><topic>Lipogenesis</topic><topic>Liver cancer</topic><topic>Metabolism</topic><topic>Nifedipine</topic><topic>Oxidation</topic><topic>Phagocytosis</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Proteinuria</topic><topic>Renal insufficiency</topic><topic>Sterol regulatory element-binding protein</topic><topic>Sterols</topic><topic>Transcription</topic><topic>Translocase</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lin, Yen-Chung</creatorcontrib><creatorcontrib>Wu, Mai-Szu</creatorcontrib><creatorcontrib>Lin, Yuh-Feng</creatorcontrib><creatorcontrib>Chen, Chang-Rong</creatorcontrib><creatorcontrib>Chen, Chang-Yu</creatorcontrib><creatorcontrib>Chen, Chang-Jui</creatorcontrib><creatorcontrib>Shen, Che-Chou</creatorcontrib><creatorcontrib>Chen, Kuan-Chou</creatorcontrib><creatorcontrib>Peng, Chiung-Chi</creatorcontrib><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>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>ProQuest Central (New)</collection><collection>ProQuest One Academic (New)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest Health & Medical Research Collection</collection><collection>ProQuest One Academic Middle East (New)</collection><collection>ProQuest One Health & Nursing</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 Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lin, Yen-Chung</au><au>Wu, Mai-Szu</au><au>Lin, Yuh-Feng</au><au>Chen, Chang-Rong</au><au>Chen, Chang-Yu</au><au>Chen, Chang-Jui</au><au>Shen, Che-Chou</au><au>Chen, Kuan-Chou</au><au>Peng, Chiung-Chi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-03-29</date><risdate>2019</risdate><volume>20</volume><issue>7</issue><spage>1570</spage><pages>1570-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Lipid accumulation in renal cells has been implicated in the pathogenesis of obesity-related kidney disease, and lipotoxicity in the kidney can be a surrogate marker for renal failure or renal fibrosis. Fatty acid oxidation provides energy to renal tubular cells. Ca
is required for mitochondrial ATP production and to decrease reactive oxygen species (ROS). However, how nifedipine (a calcium channel blocker) affects lipogenesis is unknown. We utilized rat NRK52E cells pre-treated with varying concentrations of nifedipine to examine the activity of lipogenesis enzymes and lipotoxicity. A positive control exposed to oleic acid was used for comparison. Nifedipine was found to activate acetyl Coenzyme A (CoA) synthetase, acetyl CoA carboxylase, long chain fatty acyl CoA elongase, ATP-citrate lyase, and 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase, suggesting elevated production of cholesterol and phospholipids. Nifedipine exposure induced a vast accumulation of cytosolic free fatty acids (FFA) and stimulated the production of reactive oxygen species, upregulated CD36 and KIM-1 (kidney injury molecule-1) expression, inhibited p-AMPK activity, and triggered the expression of SREBP-1/2 and lipin-1, underscoring the potential of nifedipine to induce lipotoxicity with renal damage. To our knowledge, this is the first report demonstrating nifedipine-induced lipid accumulation in the kidney.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>30934807</pmid><doi>10.3390/ijms20071570</doi><orcidid>https://orcid.org/0000-0001-7861-5054</orcidid><orcidid>https://orcid.org/0000-0002-4542-4195</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Albumins AMP-activated protein kinase Antihypertensives Apoptosis Autophagy Biosynthesis CD36 antigen Cell lines Cholesterol Fatty acids Fibrosis Hepatocytes Hepatoma Kidneys Kinases Lipids Lipogenesis Liver cancer Metabolism Nifedipine Oxidation Phagocytosis Phosphorylation Proteins Proteinuria Renal insufficiency Sterol regulatory element-binding protein Sterols Transcription Translocase |
| title | Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway |
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