{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:55:22Z","timestamp":1793840122748,"version":"4.6.1"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T00:00:00Z","timestamp":1352332800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0048952","type":"journal-article","created":{"date-parts":[[2012,11,8]],"date-time":"2012-11-08T22:54:15Z","timestamp":1352415255000},"page":"e48952","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":51,"title":["Hypoxia-Inducible Factor Activation Protects the Kidney from Gentamicin-Induced Acute Injury"],"prefix":"10.1371","volume":"7","author":[{"given":"Jeong-myung","family":"Ahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Jin","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Mi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se-Won","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-young","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sejoong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho Jun","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Wan","family":"Chae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Young","family":"Na","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2012,11,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1681\/ASN.V4181","article-title":"Can pharmacokinetic dosing decrease nephrotoxicity associated with aminoglycoside therapy","volume":"4","author":"DJ Leehey","year":"1993","journal-title":"J Am Soc Nephrol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/toxsci\/56.1.229","article-title":"Gentamicin-induced apoptosis in renal cell lines and embryonic rat fibroblasts","volume":"56","author":"M El Mouedden","year":"2000","journal-title":"Toxicol Sci"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1111\/j.1523-1755.2004.00642.x","article-title":"Gentamicin treatment induces simultaneous mesangial proliferation and apoptosis in rats","volume":"65","author":"C Mart\u00ednez-Salgado","year":"2004","journal-title":"Kidney Int"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/s10495-007-0151-z","article-title":"Renal cell apoptosis induced by nephrotoxic drugs: cellular and molecular mechanisms and potential approaches to modulation","volume":"13","author":"H Servais","year":"2008","journal-title":"Apoptosis"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/toxsci\/kfq267","article-title":"An integrative overview on the mechanisms underlying the renal tubular cytotoxicity of gentamicin","volume":"119","author":"Y Quiros","year":"2011","journal-title":"Toxicol Sci"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/S0278-6915(03)00186-8","article-title":"Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research","volume":"41","author":"BH Ali","year":"2003","journal-title":"Food Chem Toxicol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","article-title":"Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension","volume":"92","author":"GL Wang","year":"1995","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1126\/science.1059817","article-title":"HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing","volume":"292","author":"M Ivan","year":"2001","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1126\/science.1059796","article-title":"Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation","volume":"292","author":"P Jaakkola","year":"2001","journal-title":"Science"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1101\/gad.13.14.1822","article-title":"The von Hippel-Lindau tumor suppressor protein is a component of an E3 ubiquitin-protein ligase activity","volume":"13","author":"J Lisztwan","year":"1999","journal-title":"Genes Dev"},{"key":"ref11","first-page":"re12","article-title":"Integration of oxygen signaling at the consensus HRE","volume":"2005(306)","author":"RH Wenger","year":"2005","journal-title":"Sci STKE"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"40337","DOI":"10.1074\/jbc.M403057200","article-title":"Depletion of intracellular ascorbate by the carcinogenic metals nickel and cobalt results in the induction of hypoxic stress","volume":"279","author":"K Salnikow","year":"2004","journal-title":"J Biol Chem"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1681\/ASN.2005121302","article-title":"Preconditional activation of hypoxia-inducible factors ameliorates ischemic acute renal failure","volume":"17","author":"WM Bernhardt","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1681\/ASN.2007040419","article-title":"HIF activation protects from acute kidney injury","volume":"19","author":"A Weidemann","year":"2008","journal-title":"J Am Soc Nephrol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1111\/j.1523-1755.2005.00742.x","article-title":"Induction of protective genes by cobalt ameliorates tubulointerstitial injury in the progressive Thy1 nephritis","volume":"68","author":"T Tanaka","year":"2005","journal-title":"Kidney Int"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1038\/labinvest.3700328","article-title":"Cobalt promotes angiogenesis via hypoxia-inducible factor and protects tubulointerstitium in the remnant kidney model","volume":"85","author":"T Tanaka","year":"2005","journal-title":"Lab Invest"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1093\/ndt\/gfp454","article-title":"Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney","volume":"25","author":"YR Song","year":"2010","journal-title":"Nephrol Dial Transplant"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1681\/ASN.2006060639","article-title":"Protective role of hypoxia-inducible factor-2alpha against ischemic damage and oxidative stress in the kidney","volume":"18","author":"I Kojima","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/ndt\/gfm715","article-title":"Cobalt ameliorates renal injury in an obese, hypertensive type 2 diabetes rat model","volume":"23","author":"S Ohtomo","year":"2008","journal-title":"Nephrol Dial Transplant"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.1021\/tx800061w","article-title":"Integrated pathway analysis of rat urine metabolic profiles and kidney transcriptomic profiles to elucidate the systems toxicology of model nephrotoxicants","volume":"21","author":"EY Xu","year":"2008","journal-title":"Chem Res Toxicol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3319","DOI":"10.1093\/ndt\/gfp305","article-title":"Hypoxia interferes with connective tissue growth factor (CTGF) gene expression in human proximal tubular cell lines","volume":"24","author":"S Kroening","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1620\/tjem.226.197","article-title":"Activation of hypoxia-inducible factor by cobalt is associated with the attenuation of tissue injury and apoptosis in cyclosporine-induced nephropathy","volume":"226","author":"SW Oh","year":"2012","journal-title":"Tohoku J Exp Med"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1097\/01.ASN.0000074239.22357.06","article-title":"Induction of renoprotective gene expression by cobalt ameliorates ischemic injury of the kidney in rats","volume":"14","author":"M Matsumoto","year":"2003","journal-title":"J Am Soc Nephrol"},{"key":"ref24","first-page":"137","article-title":"Gentamicin and tobramycin nephrotoxicity. A morphologic and functional comparison in the rat","volume":"93","year":"1978","journal-title":"Am J Pathol"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.tibs.2006.03.004","article-title":"Apoptosomes: protease activation platforms to die from","volume":"31","author":"C Adrain","year":"2006","journal-title":"Trends Biochem Sci"},{"key":"ref26","unstructured":"Chambers HF (2006) Aminoglycoides. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman & Gilman\u2019s The Pharmacological Basis of Therapeutics, 11 edition. New York: The McGraw-Hill Companies. 1155\u20131172."},{"key":"ref27","first-page":"e109","article-title":"Antioxidants. Do they have a place in the prevention or therapy of acute kidney injury?","volume":"109","author":"JL Koyner","year":"2008","journal-title":"Nephron Exp Nephrol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1046\/j.0767-3981.2003.00211.x","article-title":"Effect of tempol (4-hydroxy tempo) on gentamicin-induced nephrotoxicity in rats","volume":"18","author":"Y Karata\u015f","year":"2004","journal-title":"Fundam Clin Pharmacol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1093\/ndt\/gfl699","article-title":"Tetramethylpyrazine protects rat renal tubular cell apoptosis induced by gentamicin","volume":"22","author":"SH Juan","year":"2007","journal-title":"Nephrol Dial Transplant"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0014-2999(02)01749-1","article-title":"A role for superoxide in gentamicin-mediated nephropathy in rats","volume":"450","author":"S Cuzzocrea","year":"2002","journal-title":"Eur J Pharmacol"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1089\/152308602762197434","article-title":"Protective effect of trans-resveratrol on gentamicin-induced nephrotoxicity","volume":"4","author":"AI Morales","year":"2002","journal-title":"Antioxid Redox Signal"},{"key":"ref32","first-page":"633","article-title":"Role of myofibroblasts, macrophages, transforming growth factor-beta endothelin, angiotensin-II, and fibronectin in the progression of tubulointerstitial nephritis induced by gentamicin","volume":"15","author":"TJ Geleilete","year":"2002","journal-title":"J Nephrol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1093\/ndt\/gfi225","article-title":"Kallikrein\/kinin protects against gentamicin-induced nephrotoxicity by inhibition of inflammation and apoptosis","volume":"21","author":"G Bledsoe","year":"2006","journal-title":"Nephrol Dial Transplant"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.ejphar.2008.12.055","article-title":"Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicininduced nephrotoxicity in Wistar rats","volume":"606","author":"S Kalayarasan","year":"2009","journal-title":"Eur J Pharmacol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/ndt\/gfn545","article-title":"Antioxidation and anti-inflammation by haem oxygenase-1 contribute to protection by tetramethylpyrazine against gentamicin-induced apoptosis in murine renal tubular cells","volume":"24","author":"YM Sue","year":"2009","journal-title":"Nephrol Dial Transplant"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/S0092-8674(03)00154-5","article-title":"HIF-1alpha is essential for myeloid cell-mediated inflammation","volume":"112","author":"T Cramer","year":"2003","journal-title":"Cell"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1172\/JCI200421086","article-title":"Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis","volume":"114","author":"J Karhausen","year":"2004","journal-title":"J Clin Invest"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1053\/j.gastro.2007.09.033","article-title":"Mucosal protection by hypoxia-inducible factor prolyl hydroxylase inhibition","volume":"134","author":"A Robinson","year":"2008","journal-title":"Gastroenterology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1053\/j.gastro.2007.10.012","article-title":"The hydroxylase inhibitor dimethyloxalylglycine is protective in a murine model of colitis","volume":"134","author":"EP Cummins","year":"2008","journal-title":"Gastroenterology"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1128\/AAC.44.3.665-675.2000","article-title":"Apoptosis in renal proximal tubules of rats treated with low doses of aminoglycosides","volume":"44","author":"M El Mouedden","year":"2000","journal-title":"Antimicrob Agents Chemother"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1038\/ki.2010.11","article-title":"Metformin prevents experimental gentamicin-induced nephropathy by a mitochondriadependent pathway","volume":"77","author":"AI Morales","year":"2010","journal-title":"Kidney Int"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1517\/13543784.2011.566861","article-title":"HIF prolyl hydroxylase inhibitors for anemia","volume":"20","author":"E Muchnik","year":"2011","journal-title":"Expert Opin Investig Drugs"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0048952","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,31]],"date-time":"2022-01-31T02:01:22Z","timestamp":1643594482000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0048952"}},"subtitle":[],"editor":[{"given":"Shree Ram","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2012,11,8]]},"references-count":42,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2012,11,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0048952","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,8]]}}}