Modulation of the ubiquitin-proteasome proteolytic pathway by eicosapentaenoic acid supplementation in a model of progressive malignancy
BACKGROUND: A benefit for eicosapentaenoic acid (EPA) supplementation for protein maintenance in cancer patients exists, although specific mechanisms are unknown. As the ubiquitin-proteasome proteolytic (UPP) pathway has been implicated in protein use in malignancy, we determined mRNA levels for UPP...
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| creator | Mikhail, AT Babcock, TA Jho, DH Helton, WS Brodsky, IG Espat, NJ |
| description | BACKGROUND: A benefit for eicosapentaenoic acid (EPA) supplementation for protein maintenance in cancer patients exists, although specific mechanisms are unknown. As the ubiquitin-proteasome proteolytic (UPP) pathway has been implicated in protein use in malignancy, we determined mRNA levels for UPP components in the liver and muscles from EPA-treated rats bearing the methylcholanthrene (MCA) fibrosarcoma. METHODS: Rats implanted with MCA tumor were divided into 3 groups on day 13: EPA (5 g/kg per day plus 10 IU vitamin E/g fat), corn oil (5 g/kg per day plus 10 IU vitamin E/g fat), and saline (5 g/kg per day plus 10 IU E/g saline). On day 29, tumor volume (TV) was determined; liver and quadriceps muscles were also excised to determine gene expression of C2, C3, E2(14k), and E3alpha by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: EPA-treated rats demonstrated a reduced TV of 21% compared with the 28% and 30% TV of corn oil- and saline-treated rats, respectively. Muscle mRNA levels of E2(14k) and E3alpha in EPA-treated animals were decreased compared with corn oil- and saline-treated animals. EPA treatment also decreased hepatic C2, C3, and E2(14k) mRNA levels compared with saline treatment. CONCLUSION: EPA supplement decreased skeletal muscle E2(14k), E3alpha, and hepatic C2 mRNA levels compared with the isocaloric, isonitrogenous corn oil supplement, supporting a treatment-specific effect. The decrease in hepatic C3 and E2(14k) mRNA levels induced by EPA were partly because of caloric benefit and partly attributable to a treatment-specific effect. Additionally, differences in the hepatic and muscle gene expressions of UPP components suggested an organ-specific effect for omega-3 fatty acid activity.
The ubiquitin-proteasome proteolytic pathway plays a large role in protein redistribution during the development of malignancy-induced cachexia. Supplementation with EPA, in a rat model of progressive malignancy, showed a potential clinical benefit by decreasing tumor volume and modulating key components of the ubiquitin-proteasome proteolytic pathway in liver and muscle tissue. |
| doi_str_mv | 10.1177/0148607103027002105 |
| format | Article |
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The ubiquitin-proteasome proteolytic pathway plays a large role in protein redistribution during the development of malignancy-induced cachexia. Supplementation with EPA, in a rat model of progressive malignancy, showed a potential clinical benefit by decreasing tumor volume and modulating key components of the ubiquitin-proteasome proteolytic pathway in liver and muscle tissue.</description><identifier>ISSN: 0148-6071</identifier><identifier>EISSN: 1941-2444</identifier><identifier>DOI: 10.1177/0148607103027002105</identifier><identifier>PMID: 12665165</identifier><identifier>CODEN: JPENDU</identifier><language>eng</language><publisher>London, England: SAGE Publications</publisher><subject>Animals ; Biological and medical sciences ; Cysteine Endopeptidases - genetics ; Cysteine Endopeptidases - metabolism ; Dietary Supplements ; Disease Models, Animal ; Eicosapentaenoic Acid - administration & dosage ; Eicosapentaenoic Acid - pharmacology ; Fibrosarcoma - diet therapy ; Fibrosarcoma - metabolism ; Gene Expression Regulation, Enzymologic ; General and cellular metabolism. Vitamins ; Liver - chemistry ; Liver - drug effects ; Medical sciences ; Multienzyme Complexes - genetics ; Multienzyme Complexes - metabolism ; Muscle, Skeletal - chemistry ; Muscle, Skeletal - drug effects ; Organ Specificity ; Pharmacology. Drug treatments ; Proteasome Endopeptidase Complex ; Random Allocation ; Rats ; Rats, Inbred F344 ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - analysis ; Ubiquitin - genetics ; Ubiquitin - metabolism</subject><ispartof>JPEN. Journal of parenteral and enteral nutrition, 2003-03, Vol.27 (2), p.105-109</ispartof><rights>2003 by The American Society for Parenteral and Enteral Nutrition</rights><rights>2003 INIST-CNRS</rights><rights>Copyright American Society for Parenteral and Enteral Nutrition Mar/Apr 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4495-64c9d40aa17cba131b406b9b19f3d5a02de0ecc058e79e43da6be7beffd158993</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1177%2F0148607103027002105$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1177%2F0148607103027002105$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14618424$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12665165$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mikhail, AT</creatorcontrib><creatorcontrib>Babcock, TA</creatorcontrib><creatorcontrib>Jho, DH</creatorcontrib><creatorcontrib>Helton, WS</creatorcontrib><creatorcontrib>Brodsky, IG</creatorcontrib><creatorcontrib>Espat, NJ</creatorcontrib><title>Modulation of the ubiquitin-proteasome proteolytic pathway by eicosapentaenoic acid supplementation in a model of progressive malignancy</title><title>JPEN. Journal of parenteral and enteral nutrition</title><addtitle>JPEN J Parenter Enteral Nutr</addtitle><description>BACKGROUND: A benefit for eicosapentaenoic acid (EPA) supplementation for protein maintenance in cancer patients exists, although specific mechanisms are unknown. As the ubiquitin-proteasome proteolytic (UPP) pathway has been implicated in protein use in malignancy, we determined mRNA levels for UPP components in the liver and muscles from EPA-treated rats bearing the methylcholanthrene (MCA) fibrosarcoma. METHODS: Rats implanted with MCA tumor were divided into 3 groups on day 13: EPA (5 g/kg per day plus 10 IU vitamin E/g fat), corn oil (5 g/kg per day plus 10 IU vitamin E/g fat), and saline (5 g/kg per day plus 10 IU E/g saline). On day 29, tumor volume (TV) was determined; liver and quadriceps muscles were also excised to determine gene expression of C2, C3, E2(14k), and E3alpha by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: EPA-treated rats demonstrated a reduced TV of 21% compared with the 28% and 30% TV of corn oil- and saline-treated rats, respectively. Muscle mRNA levels of E2(14k) and E3alpha in EPA-treated animals were decreased compared with corn oil- and saline-treated animals. EPA treatment also decreased hepatic C2, C3, and E2(14k) mRNA levels compared with saline treatment. CONCLUSION: EPA supplement decreased skeletal muscle E2(14k), E3alpha, and hepatic C2 mRNA levels compared with the isocaloric, isonitrogenous corn oil supplement, supporting a treatment-specific effect. The decrease in hepatic C3 and E2(14k) mRNA levels induced by EPA were partly because of caloric benefit and partly attributable to a treatment-specific effect. Additionally, differences in the hepatic and muscle gene expressions of UPP components suggested an organ-specific effect for omega-3 fatty acid activity.
The ubiquitin-proteasome proteolytic pathway plays a large role in protein redistribution during the development of malignancy-induced cachexia. Supplementation with EPA, in a rat model of progressive malignancy, showed a potential clinical benefit by decreasing tumor volume and modulating key components of the ubiquitin-proteasome proteolytic pathway in liver and muscle tissue.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cysteine Endopeptidases - genetics</subject><subject>Cysteine Endopeptidases - metabolism</subject><subject>Dietary Supplements</subject><subject>Disease Models, Animal</subject><subject>Eicosapentaenoic Acid - administration & dosage</subject><subject>Eicosapentaenoic Acid - pharmacology</subject><subject>Fibrosarcoma - diet therapy</subject><subject>Fibrosarcoma - metabolism</subject><subject>Gene Expression Regulation, Enzymologic</subject><subject>General and cellular metabolism. Vitamins</subject><subject>Liver - chemistry</subject><subject>Liver - drug effects</subject><subject>Medical sciences</subject><subject>Multienzyme Complexes - genetics</subject><subject>Multienzyme Complexes - metabolism</subject><subject>Muscle, Skeletal - chemistry</subject><subject>Muscle, Skeletal - drug effects</subject><subject>Organ Specificity</subject><subject>Pharmacology. Drug treatments</subject><subject>Proteasome Endopeptidase Complex</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - analysis</subject><subject>Ubiquitin - genetics</subject><subject>Ubiquitin - metabolism</subject><issn>0148-6071</issn><issn>1941-2444</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkd1u1DAQhS0EotvCEyAhCwnuAjOJk6wvUVUoqPxcwHU0cSZbV06cxkmrvAGPjdNdaSWEEFe2PN-cOT4jxAuEt4hl-Q5QbQsoETJIS4AUIX8kNqgVJqlS6rHYrESyIifiNIQbAMgKgKfiBNOiyLHIN-LXF9_Mjibre-lbOV2znGt7O9vJ9skw-okp-I7lw9W7ZbJGDjRd39Mi60WyNT7QwP1E3PtYI2MbGeZhcNytrw_CtpckO9-wW2dEqd3IIdg7lh05u-upN8sz8aQlF_j54TwTPz9c_Di_TK6-ffx0_v4qMUrpPCmU0Y0CIixNTZhhraCodY26zZqcIG0Y2BjIt1xqVllDRc1lzW3bYL7VOjsTb_a60cbtzGGqOhsMO0c9-zlUZYaZjjlF8NUf4I2fxz56q9KYOGqNaYSyPWRGH8LIbTWMtqNxqRCqdUvVX7YUu14epOe64-bYc1hLBF4fAAqGXDvGhGw4cqrArUpV5PSeu7eOl_-ZXX3-fvEV9iZg3xtox8e__cv3b4THuok</recordid><startdate>200303</startdate><enddate>200303</enddate><creator>Mikhail, AT</creator><creator>Babcock, TA</creator><creator>Jho, DH</creator><creator>Helton, WS</creator><creator>Brodsky, IG</creator><creator>Espat, NJ</creator><general>SAGE Publications</general><general>ASPEN</general><general>American Society for Parenteral and Enteral Nutrition</general><scope>IQODW</scope><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>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>200303</creationdate><title>Modulation of the ubiquitin-proteasome proteolytic pathway by eicosapentaenoic acid supplementation in a model of progressive malignancy</title><author>Mikhail, AT ; Babcock, TA ; Jho, DH ; Helton, WS ; Brodsky, IG ; Espat, NJ</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4495-64c9d40aa17cba131b406b9b19f3d5a02de0ecc058e79e43da6be7beffd158993</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cysteine Endopeptidases - genetics</topic><topic>Cysteine Endopeptidases - metabolism</topic><topic>Dietary Supplements</topic><topic>Disease Models, Animal</topic><topic>Eicosapentaenoic Acid - administration & dosage</topic><topic>Eicosapentaenoic Acid - pharmacology</topic><topic>Fibrosarcoma - diet therapy</topic><topic>Fibrosarcoma - metabolism</topic><topic>Gene Expression Regulation, Enzymologic</topic><topic>General and cellular metabolism. Vitamins</topic><topic>Liver - chemistry</topic><topic>Liver - drug effects</topic><topic>Medical sciences</topic><topic>Multienzyme Complexes - genetics</topic><topic>Multienzyme Complexes - metabolism</topic><topic>Muscle, Skeletal - chemistry</topic><topic>Muscle, Skeletal - drug effects</topic><topic>Organ Specificity</topic><topic>Pharmacology. Drug treatments</topic><topic>Proteasome Endopeptidase Complex</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - analysis</topic><topic>Ubiquitin - genetics</topic><topic>Ubiquitin - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mikhail, AT</creatorcontrib><creatorcontrib>Babcock, TA</creatorcontrib><creatorcontrib>Jho, DH</creatorcontrib><creatorcontrib>Helton, WS</creatorcontrib><creatorcontrib>Brodsky, IG</creatorcontrib><creatorcontrib>Espat, NJ</creatorcontrib><collection>Pascal-Francis</collection><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>Nursing & Allied Health Database</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>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>eLibrary</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</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>MEDLINE - Academic</collection><jtitle>JPEN. Journal of parenteral and enteral nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mikhail, AT</au><au>Babcock, TA</au><au>Jho, DH</au><au>Helton, WS</au><au>Brodsky, IG</au><au>Espat, NJ</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modulation of the ubiquitin-proteasome proteolytic pathway by eicosapentaenoic acid supplementation in a model of progressive malignancy</atitle><jtitle>JPEN. Journal of parenteral and enteral nutrition</jtitle><addtitle>JPEN J Parenter Enteral Nutr</addtitle><date>2003-03</date><risdate>2003</risdate><volume>27</volume><issue>2</issue><spage>105</spage><epage>109</epage><pages>105-109</pages><issn>0148-6071</issn><eissn>1941-2444</eissn><coden>JPENDU</coden><abstract>BACKGROUND: A benefit for eicosapentaenoic acid (EPA) supplementation for protein maintenance in cancer patients exists, although specific mechanisms are unknown. As the ubiquitin-proteasome proteolytic (UPP) pathway has been implicated in protein use in malignancy, we determined mRNA levels for UPP components in the liver and muscles from EPA-treated rats bearing the methylcholanthrene (MCA) fibrosarcoma. METHODS: Rats implanted with MCA tumor were divided into 3 groups on day 13: EPA (5 g/kg per day plus 10 IU vitamin E/g fat), corn oil (5 g/kg per day plus 10 IU vitamin E/g fat), and saline (5 g/kg per day plus 10 IU E/g saline). On day 29, tumor volume (TV) was determined; liver and quadriceps muscles were also excised to determine gene expression of C2, C3, E2(14k), and E3alpha by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: EPA-treated rats demonstrated a reduced TV of 21% compared with the 28% and 30% TV of corn oil- and saline-treated rats, respectively. Muscle mRNA levels of E2(14k) and E3alpha in EPA-treated animals were decreased compared with corn oil- and saline-treated animals. EPA treatment also decreased hepatic C2, C3, and E2(14k) mRNA levels compared with saline treatment. CONCLUSION: EPA supplement decreased skeletal muscle E2(14k), E3alpha, and hepatic C2 mRNA levels compared with the isocaloric, isonitrogenous corn oil supplement, supporting a treatment-specific effect. The decrease in hepatic C3 and E2(14k) mRNA levels induced by EPA were partly because of caloric benefit and partly attributable to a treatment-specific effect. Additionally, differences in the hepatic and muscle gene expressions of UPP components suggested an organ-specific effect for omega-3 fatty acid activity.
The ubiquitin-proteasome proteolytic pathway plays a large role in protein redistribution during the development of malignancy-induced cachexia. Supplementation with EPA, in a rat model of progressive malignancy, showed a potential clinical benefit by decreasing tumor volume and modulating key components of the ubiquitin-proteasome proteolytic pathway in liver and muscle tissue.</abstract><cop>London, England</cop><pub>SAGE Publications</pub><pmid>12665165</pmid><doi>10.1177/0148607103027002105</doi><tpages>5</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Cysteine Endopeptidases - genetics Cysteine Endopeptidases - metabolism Dietary Supplements Disease Models, Animal Eicosapentaenoic Acid - administration & dosage Eicosapentaenoic Acid - pharmacology Fibrosarcoma - diet therapy Fibrosarcoma - metabolism Gene Expression Regulation, Enzymologic General and cellular metabolism. Vitamins Liver - chemistry Liver - drug effects Medical sciences Multienzyme Complexes - genetics Multienzyme Complexes - metabolism Muscle, Skeletal - chemistry Muscle, Skeletal - drug effects Organ Specificity Pharmacology. Drug treatments Proteasome Endopeptidase Complex Random Allocation Rats Rats, Inbred F344 Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Ubiquitin - genetics Ubiquitin - metabolism |
| title | Modulation of the ubiquitin-proteasome proteolytic pathway by eicosapentaenoic acid supplementation in a model of progressive malignancy |
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