{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:16:51Z","timestamp":1762157811968},"reference-count":72,"publisher":"American Physiological Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2019,9,1]]},"abstract":"<jats:p> Mitochondrial dysfunction and oxidative stress have been implicated in cyclosporin A (CsA)-induced nephrotoxicity. CsA interacts with cyclophilin D (CypD), an essential component of the mitochondrial permeability transition pore and regulator of cell death processes. Controversial reports have suggested that CypD deletion may or may not protect cells against oxidative stress-induced cell death. In the present study, we treated wild-type (WT) mice and mice lacking CypD [peptidylprolyl isomerase F knockout ( Ppif<jats:sup>\u2212\/\u2212<\/jats:sup>) mice] with CsA to test the role and contribution of CypD to the widely described CsA-induced renal toxicity and oxidative stress. Our results showed an increase in the levels of several known uremic toxins as well as the oxidative stress markers PGF<jats:sub>2\u03b1<\/jats:sub> and 8-isoprostane in CsA-treated WT animals but not in Ppif<jats:sup>\u2212\/\u2212<\/jats:sup> animals. Similarly, a decline in S-adenosylmethionine and the resulting methylation potential indicative of DNA hypomethylation were observed only in CsA-treated WT mice. This confirms previous reports of the protective effects of CypD deletion on the mouse kidney mediated through a stronger resistance of these animals to oxidative stress and DNA methylation damage. However, a negative effect of CsA on the glycolysis and overall energy metabolism in Ppif<jats:sup>\u2212\/\u2212<\/jats:sup> mice also indicated that additional, CypD-parallel pathways are involved in the toxic effects of CsA on the kidney. In summary, CsA-mediated induction of oxidative stress is associated with CypD, with CypD deletion providing a protective effect, whereas the reduction of energy production observed upon CsA exposure did not depend on the animals\u2019 CypD status. <\/jats:p>","DOI":"10.1152\/ajprenal.00417.2018","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T09:37:15Z","timestamp":1560332235000},"page":"F683-F694","source":"Crossref","is-referenced-by-count":14,"title":["Cyclophilin D knockout protects the mouse kidney against cyclosporin A-induced oxidative stress"],"prefix":"10.1152","volume":"317","author":[{"given":"Jelena","family":"Klawitter","sequence":"first","affiliation":[{"name":"Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado"},{"name":"Division of Nephrology and Hypertension, Department of Medicine, University of Colorado Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jost","family":"Klawitter","sequence":"additional","affiliation":[{"name":"Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Pennington","sequence":"additional","affiliation":[{"name":"Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bruce","family":"Kirkpatrick","sequence":"additional","affiliation":[{"name":"Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galen","family":"Roda","sequence":"additional","affiliation":[{"name":"Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nidhi C.","family":"Kotecha","sequence":"additional","affiliation":[{"name":"Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joshua M.","family":"Thurman","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Hypertension, Department of Medicine, University of Colorado Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe","family":"Christians","sequence":"additional","affiliation":[{"name":"Clinical Research and Development, Department of Anesthesiology, University of Colorado Denver, Aurora, Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000151290.04952.3B"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.003200"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nature03434"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C500089200"},{"key":"B5","first-page":"SS42","volume":"71","author":"Campistol JM","year":"2001","journal-title":"Transplantation"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0705939"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00239.2009"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12841"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013121283"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-13-0321"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43171"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-579X(02)00059-7"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2017.05.022"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/352803a0"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0175242"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1097\/01.tp.0000251423.78124.51"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63430-X"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201400053"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2006.078972"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(02)00455-8"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1159\/000316704"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.112862"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.08.003"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2011.01.062"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2017.10.009"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1081\/JDI-120039812"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1021\/tx800253x"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03689.x"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1021\/pr900761m"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/pr300260e"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10076-9"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00327.2014"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2007.03.018"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.25947"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2016.00165"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/584758"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-011-0897-z"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200205151-00003"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198908033210504"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90124-H"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.2217\/14796678.1.4.457"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2004.00515.x"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2012.12.004"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-017-0770-x"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nature03317"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2014.07.008"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2828(91)90181-K"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.487"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00944.x"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199512000-00017"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.09.008"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2007.05.009"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp126"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00033.2011"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05634.x"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18112283"},{"key":"B57","first-page":"453","volume":"18","author":"Redondo-Horcajo M","year":"2005","journal-title":"J Nephrol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0505294102"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1159\/000209208"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1126\/science.1081208"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1159\/000186431"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-2277.2011.01265.x"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1515\/cclm.1992.30.6.325"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.305360"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1038\/srep15981"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2006.05.002"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.03.053"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2017.03.003"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2004.08.109"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1159\/000345988"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2012.024"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1038\/pcan.2014.45"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00417.2018","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T09:37:58Z","timestamp":1568021878000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00417.2018"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,1]]},"references-count":72,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,9,1]]}},"alternative-id":["10.1152\/ajprenal.00417.2018"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00417.2018","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,9,1]]}}}