Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action
Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5′-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumi...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2009-11, Vol.389 (1), p.187-192 |
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| creator | Lim, Han Wern Lim, Hwee Ying Wong, Kim Ping |
| description | Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5′-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F0F1-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F0F1-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling. |
| doi_str_mv | 10.1016/j.bbrc.2009.08.121 |
| format | Article |
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Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5′-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F0F1-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F0F1-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. 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Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5′-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F0F1-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F0F1-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. The resulting change in ATP:AMP could disrupt the phosphorylation status of the cell; this provides a possible mechanism for its activation of AMPK and its downstream mTOR and STAT-3 signaling.</description><subject>6-Ketocholestanol</subject><subject>60 APPLIED LIFE SCIENCES</subject><subject>ADENINES</subject><subject>Adenosine Triphosphate - biosynthesis</subject><subject>Adolescent</subject><subject>AMP</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>ANTIOXIDANTS</subject><subject>Antioxidants - pharmacology</subject><subject>ANTS</subject><subject>ATP</subject><subject>BIOSYNTHESIS</subject><subject>CARBONYLS</subject><subject>Cell Line, Tumor</subject><subject>CONCENTRATION RATIO</subject><subject>CURCUMIN</subject><subject>Curcumin - pharmacology</subject><subject>CYANIDES</subject><subject>DINITROPHENOL</subject><subject>F0F1-ATPase</subject><subject>Humans</subject><subject>INFLAMMATION</subject><subject>LIVER</subject><subject>Male</subject><subject>MITOCHONDRIA</subject><subject>Mitochondria, Liver - drug effects</subject><subject>Mitochondria, Liver - enzymology</subject><subject>NEOPLASMS</subject><subject>OXIDATION</subject><subject>Oxidative Phosphorylation - drug effects</subject><subject>PERMEABILITY</subject><subject>PHOSPHORYLATION</subject><subject>Proton-Translocating ATPases - metabolism</subject><subject>Protonophore</subject><subject>RATS</subject><subject>Rats, Wistar</subject><subject>RESPIRATION</subject><subject>Respiratory inhibitor</subject><subject>Uncoupler</subject><subject>Uncoupling Agents - pharmacology</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFr3DAQhUVpSbZp_kAPxVDIze6MIstW6aWENA0EemmgNyFLcqPFlraSHbr_vhJe6C0HMYj53uMxj5D3CA0C8k_7ZhiibiiAaKBvkOIrskMQUFME9prsAIDXVOCvc_I2pT0AIuPijJyj6LDlHdsR8-h1WA-T87-rMFbhrzNqcc-2OjyFlF88TvkffDUcK71Gvc7Of67u56zQ2yKr3JIqbadpnVSsZquflHdpLhulC_OOvBnVlOzlaV6Qx2-3P2--1w8_7u5vvj7UmrF-qdveWGbQ9KpTwNm1aDsL3ArNaM97Y1Q7dmYANLZVPXJOGXDNxnFoObCe4fUF-bj5hrQ4mbRbchYdvLd6kZSiENknU1cbdYjhz2rTImeXSnzlbViT5B3nvO2KHd1AHUNK0Y7yEN2s4lEiyNKA3MvSgCwNSOhlbiCLPpzc12G25r_kdPIMfNkAmy_x7GwsQa3X1rhYcprgXvL_B6pTmCY</recordid><startdate>20091106</startdate><enddate>20091106</enddate><creator>Lim, Han Wern</creator><creator>Lim, Hwee Ying</creator><creator>Wong, Kim Ping</creator><general>Elsevier Inc</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>7X8</scope><scope>OTOTI</scope></search><sort><creationdate>20091106</creationdate><title>Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action</title><author>Lim, Han Wern ; Lim, Hwee Ying ; Wong, Kim Ping</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-58de4d1d8a7a0643957e06e9c42868dda5f7db01de5a81662406c4ffb56048413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>6-Ketocholestanol</topic><topic>60 APPLIED LIFE SCIENCES</topic><topic>ADENINES</topic><topic>Adenosine Triphosphate - biosynthesis</topic><topic>Adolescent</topic><topic>AMP</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents, Non-Steroidal - pharmacology</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>ANTIOXIDANTS</topic><topic>Antioxidants - pharmacology</topic><topic>ANTS</topic><topic>ATP</topic><topic>BIOSYNTHESIS</topic><topic>CARBONYLS</topic><topic>Cell Line, Tumor</topic><topic>CONCENTRATION RATIO</topic><topic>CURCUMIN</topic><topic>Curcumin - pharmacology</topic><topic>CYANIDES</topic><topic>DINITROPHENOL</topic><topic>F0F1-ATPase</topic><topic>Humans</topic><topic>INFLAMMATION</topic><topic>LIVER</topic><topic>Male</topic><topic>MITOCHONDRIA</topic><topic>Mitochondria, Liver - drug effects</topic><topic>Mitochondria, Liver - enzymology</topic><topic>NEOPLASMS</topic><topic>OXIDATION</topic><topic>Oxidative Phosphorylation - drug effects</topic><topic>PERMEABILITY</topic><topic>PHOSPHORYLATION</topic><topic>Proton-Translocating ATPases - metabolism</topic><topic>Protonophore</topic><topic>RATS</topic><topic>Rats, Wistar</topic><topic>RESPIRATION</topic><topic>Respiratory inhibitor</topic><topic>Uncoupler</topic><topic>Uncoupling Agents - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lim, Han Wern</creatorcontrib><creatorcontrib>Lim, Hwee Ying</creatorcontrib><creatorcontrib>Wong, Kim Ping</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lim, Han Wern</au><au>Lim, Hwee Ying</au><au>Wong, Kim Ping</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2009-11-06</date><risdate>2009</risdate><volume>389</volume><issue>1</issue><spage>187</spage><epage>192</epage><pages>187-192</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>Curcumin is a phytochemical isolated from the rhizome of turmeric. Recent reports have shown curcumin to have antioxidant, anti-inflammatory and anti-tumor properties as well as affecting the 5′-AMP activated protein kinase (AMPK), mTOR and STAT-3 signaling pathways. We provide evidence that curcumin acts as an uncoupler. Well-established biochemical techniques were performed on isolated rat liver mitochondria in measuring oxygen consumption, F0F1-ATPase activity and ATP biosynthesis. Curcumin displays all the characteristics typical of classical uncouplers like fccP and 2,4-dinitrophenol. In addition, at concentrations higher than 50μM, curcumin was found to inhibit mitochondrial respiration which is a characteristic feature of inhibitory uncouplers. As a protonophoric uncoupler and as an activator of F0F1-ATPase, curcumin causes a decrease in ATP biosynthesis in rat liver mitochondria. 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| subjects | 6-Ketocholestanol 60 APPLIED LIFE SCIENCES ADENINES Adenosine Triphosphate - biosynthesis Adolescent AMP Animals Anti-Inflammatory Agents, Non-Steroidal - pharmacology Antineoplastic Agents - pharmacology ANTIOXIDANTS Antioxidants - pharmacology ANTS ATP BIOSYNTHESIS CARBONYLS Cell Line, Tumor CONCENTRATION RATIO CURCUMIN Curcumin - pharmacology CYANIDES DINITROPHENOL F0F1-ATPase Humans INFLAMMATION LIVER Male MITOCHONDRIA Mitochondria, Liver - drug effects Mitochondria, Liver - enzymology NEOPLASMS OXIDATION Oxidative Phosphorylation - drug effects PERMEABILITY PHOSPHORYLATION Proton-Translocating ATPases - metabolism Protonophore RATS Rats, Wistar RESPIRATION Respiratory inhibitor Uncoupler Uncoupling Agents - pharmacology |
| title | Uncoupling of oxidative phosphorylation by curcumin: Implication of its cellular mechanism of action |
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