{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:21:33Z","timestamp":1787167293706,"version":"build-2736575974"},"reference-count":34,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)","doi-asserted-by":"publisher","award":["T32 CA108459"],"award-info":[{"award-number":["T32 CA108459"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"HHS | NIH | National Institute of Environmental Health Sciences (NIEHS)","doi-asserted-by":"publisher","award":["R01 ES002710"],"award-info":[{"award-number":["R01 ES002710"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute (NCI)","doi-asserted-by":"publisher","award":["1R03CA181837-01"],"award-info":[{"award-number":["1R03CA181837-01"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NIH national cancer Institute","doi-asserted-by":"crossref","award":["1R01CA135401-01A1"],"award-info":[{"award-number":["1R01CA135401-01A1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["1R01DK082690-01A1"],"award-info":[{"award-number":["1R01DK082690-01A1"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["P30 DK074038"],"award-info":[{"award-number":["P30 DK074038"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2015,9,15]]},"abstract":"<jats:p>\n                    Since polycystic kidney disease (PKD) was first noted over 30 years ago to have neoplastic parallels, there has been a resurgent interest in elucidating neoplasia-relevant pathways in PKD. Taking a nontargeted metabolomics approach in the B6(Cg)- Cys1\n                    <jats:sup>cpk\/<\/jats:sup>\n                    J ( cpk) mouse model of recessive PKD, we have now characterized metabolic reprogramming in these tissues, leading to a glutamine-dependent TCA cycle shunt toward total 2-hydroxyglutarate (2-HG) production in cpk compared with B6 wild-type kidney tissue. After confirmation of increased 2-HG expression in immortalized collecting duct cpk cells as well as in human autosomal recessive PKD tissue using targeted analysis, we show that the increase in 2-HG is likely due to glutamine-sourced \u03b1-ketoglutarate. In addition, cpk cells require exogenous glutamine for growth such that inhibition of glutaminase-1 decreases cell viability as well as proliferation. This study is a demonstration of the striking parallels between recessive PKD and cancer metabolism. Our data, once confirmed in other PKD models, suggest that future therapeutic approaches targeting this pathway, such as using glutaminase inhibitors, have the potential to open novel treatment options for renal cystic disease.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00238.2015","type":"journal-article","created":{"date-parts":[[2015,7,8]],"date-time":"2015-07-08T22:05:51Z","timestamp":1436393151000},"page":"F492-F498","source":"Crossref","is-referenced-by-count":41,"title":["The\n                    <i>cpk<\/i>\n                    model of recessive PKD shows glutamine dependence associated with the production of the oncometabolite 2-hydroxyglutarate"],"prefix":"10.1152","volume":"309","author":[{"given":"Vicki J.","family":"Hwang","sequence":"first","affiliation":[{"name":"Graduate Group in Integrative Genetics and Genomics, University of California, Davis, California;"},{"name":"Division of Nephrology, Department of Internal Medicine, University of California, Davis, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of California, Davis, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Rand","sequence":"additional","affiliation":[{"name":"Department of Entomology, University of California, Davis, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaozhe","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Translational Science, Children's National Health System, Washington, District of Columbia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Sturdivant","sequence":"additional","affiliation":[{"name":"Metabolon, Durham, North Carolina;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce","family":"Hammock","sequence":"additional","affiliation":[{"name":"Department of Entomology, University of California, Davis, California;"},{"name":"Cancer Center, University of California, Davis, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Darwin","family":"Bell","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Medical University of South Carolina and Ralph Johnson Veterans Affairs Medical Center, Charleston, South Carolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M.","family":"Guay-Woodford","sequence":"additional","affiliation":[{"name":"Center for Translational Science, Children's National Health System, Washington, District of Columbia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Graduate Group in Integrative Genetics and Genomics, University of California, Davis, California;"},{"name":"Division of Nephrology, Department of Internal Medicine, University of California, Davis, California;"},{"name":"Cancer Center, University of California, Davis, California;"},{"name":"Medical Service, Sacramento Veterans Affairs Medical Center, Sacramento, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05348"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08617"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709747104"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/1758-2946-2-9"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1021\/cb500683c"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.11.015"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.02.002"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3105"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(12)80507-5"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00195.2003"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69600"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.12.9.17680"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(66)90485-2"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nature10860"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nature10602"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/nature10642"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1159\/000184590"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2369-8-12"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164382"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.575183"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3092"},{"key":"B22","author":"Seeger-Nukpezah T","journal-title":"Nat Rev Nephrol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0696"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00183.2010"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1086\/427890"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00406.2014"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00722.2009"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71180"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2010.113"},{"key":"B30","author":"Wettersten HI","journal-title":"Cancer Res"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2010.05.003"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1117773108"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2010.12.014"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808710"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00238.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T21:19:26Z","timestamp":1567977566000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00238.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9,15]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,9,15]]}},"alternative-id":["10.1152\/ajprenal.00238.2015"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00238.2015","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9,15]]}}}