{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:33:01Z","timestamp":1791318781847,"version":"4.3.1"},"reference-count":49,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2005,11]]},"abstract":"<jats:p>Low oxygen levels (hypoxia) play a role in clinical conditions such as stroke, chronic ischemia, and cancer. To better understand these diseases, it is crucial to study the responses of vertebrates to hypoxia. Among vertebrates, some teleosts have developed the ability to adapt to extremely low oxygen levels. We have studied long-term adaptive responses to hypoxia in adult zebrafish. We used zebrafish that survived severe hypoxic conditions for 3 wk and showed adaptive behavioral and phenotypic changes. We used cDNA microarrays to investigate hypoxia-induced changes in expression of 15,532 genes in the respiratory organs (the gills). We have identified 367 differentially expressed genes of which 117 showed hypoxia-induced and 250 hypoxia-reduced expressions. Metabolic depression was indicated by repression of genes in the TCA cycle in the electron transport chain and of genes involved in protein biosynthesis. We observed enhanced expression of the monocarboxylate transporter and of the oxygen transporter myoglobin. The hypoxia-induced group further included the genes for Niemann-Pick C disease and for Wolman disease [lysosomal acid lipase (LAL)]. Both diseases lead to a similar intra- and extracellular accumulation of cholesterol and glycolipids. The Niemann-Pick C protein binds to cholesterol from internal lysosomal membranes and is involved in cholesterol trafficking. LAL is responsible for lysosomal cholesterol degradation. Our data suggest a novel adaptive mechanism to hypoxia, the induction of genes for lysosomal lipid trafficking and degradation. Studying physiological responses to hypoxia in species tolerant for extremely low oxygen levels can help identify novel regulatory genes, which may have important clinical implications.<\/jats:p>","DOI":"10.1152\/ajpregu.00089.2005","type":"journal-article","created":{"date-parts":[[2005,7,2]],"date-time":"2005-07-02T00:15:54Z","timestamp":1120263354000},"page":"R1512-R1519","source":"Crossref","is-referenced-by-count":171,"title":["Gene expression profiling of the long-term adaptive response to hypoxia in the gills of adult zebrafish"],"prefix":"10.1152","volume":"289","author":[{"given":"David L. M.","family":"van der Meer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido E. E. J. M.","family":"van den Thillart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans","family":"Witte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merijn A. G.","family":"de Bakker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Besser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael K.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herman P.","family":"Spaink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelani T. D.","family":"Leito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph P.","family":"Bagowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/93.14.1062"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.16.6263"},{"key":"R3","unstructured":"Blagosklonny MV.Hypoxia-inducible factor: Achilles\u2019 heel of antiangiogenic cancer therapy.Int J Oncol19: 257\u2013262, 2001."},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63160-4"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406613200"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1046\/j.1461-0248.2000.00160.x"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.3354\/meps111017"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.59.1.110"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1006\/mgme.1998.2707"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1139\/y03-049"},{"key":"R11","doi-asserted-by":"crossref","unstructured":"Eisen MB, Spellman PT, Brown PO, and Botstein D.Cluster analysis and display of genome-wide expression patterns.Genetics95: 14863\u201314868, 1998.","DOI":"10.1073\/pnas.95.25.14863"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1017\/S0033583503003883"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1299.126"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/S1053-4296(96)80035-X"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.4.1993"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1016\/S1532-0456(02)00080-7"},{"key":"R18","unstructured":"Hohfeld J.Regulation of the heat shock conjugate Hsc70 in the mammalian cell: the characterization of the anti-apoptotic protein BAG-1 provides novel insights.J Biol Chem3: 269\u2013274, 1998."},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1097\/00019052-199512000-00017"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1080\/07853890310017161"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2003.18.10.1916"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg086"},{"key":"R23","doi-asserted-by":"crossref","unstructured":"Lamberti A, Caraglia M, Longo O, Marra M, Abbruzzese A, and Arcari P.The translation elongation factor 1A in tumorigenesis, signal transduction and apoptosis.Amino Acids26: 443\u2013448, 2004.","DOI":"10.1007\/s00726-004-0088-2"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.3.1265"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.9.6560"},{"key":"R26","doi-asserted-by":"crossref","unstructured":"Meijer AH, Verbeek FJ, Salas-Vidal E, Corredor-Adamez M, Bussman J, van der Saar A, Otto GW, Geisler R, and Spaink HP.Transcriptome profiling of adult zebrafish at the late stage of chronic tuberculosis due toMycobacterium marinuminfection.Mol Immunol42: 185\u2013203, 2005.","DOI":"10.1016\/j.molimm.2004.11.014"},{"key":"R27","unstructured":"Mitchell GA, Kassovska-Bratinova S, Boukaftane Y, Robert MF, Wang SP, Ashmarina L, Lambert M, Lapierre P, and Potier E.Medical aspects of ketone body metabolism.Clin Invest Med18: 193\u2013216, 1995."},{"key":"R28","doi-asserted-by":"publisher","DOI":"10.1016\/j.resp.2004.01.011"},{"key":"R29","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00221.2003"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.131213198"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2004.08.013"},{"key":"R33","unstructured":"Redon R, Hussenet T, Bour G, Caulee K, Jost B, Muller D, Abecassis J, and du Manoir S.Amplicon mapping and transcriptional analysis pinpoint cyclin L as a candidate oncogene in head and neck cancer.Cancer Res62: 6211\u20136217, 2002."},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1002\/1097-010X(20010401\/30)289:4<266::AID-JEZ7>3.0.CO;2-5"},{"key":"R35","unstructured":"Robinson Gand Gray T.Electron Microscopy 3: Theory and Practice of Histology Techniques(3rd ed.). Edited by Bancroft JD and Stevens A. London: Churchill Livingstone, 1990, p. 563\u2013581."},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1007\/0-306-46825-5_12"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.12.7499"},{"key":"R38","unstructured":"Sidell BD.Intracellular oxygen diffusion: the roles of myoglobin and lipid at cold body temperature.J Exp Biol201: 1119\u20131128, 1998."},{"key":"R39","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.00594"},{"key":"R40","doi-asserted-by":"publisher","DOI":"10.1042\/bj3460281"},{"key":"R40A","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng020"},{"key":"R42","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)02010-7"},{"key":"R43","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00128.2002"},{"key":"R44","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204235"},{"key":"R44A","doi-asserted-by":"publisher","DOI":"10.3354\/meps104109"},{"key":"R44B","doi-asserted-by":"publisher","DOI":"10.1006\/hbeh.1996.0012"},{"key":"R45","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-8966(02)00065-2"},{"key":"R46","unstructured":"Witte F, Wanink JH, Rutjes HA, van der Meer HJ, and van den Thillart GEEJM.Eutrophication and the fish fauna of Lake Victoria. In:Tropical Eutrophic Lakes: Their Restoration and Management. Edited by Vikram Reddy M. New Delhi: Oxford, 2005."},{"key":"R47","doi-asserted-by":"crossref","unstructured":"Zani VJ, Asou N, Jadayel D, Heward JM, Shipley J, Nacheva E, Takasuki K, Catovsky D, and Dyer MJ.Molecular cloning of complex chromosomal translocation t(8,14,12)(q24.1;q323;q241) in a Burkitt lymphoma cell line defines a new gene (BCL7A) with homology to caldesmon.Blood87: 3124\u20133134, 1996.","DOI":"10.1182\/blood.V87.8.3124.bloodjournal8783124"},{"key":"R48","doi-asserted-by":"publisher","DOI":"10.1007\/s003600000149"},{"key":"R49","doi-asserted-by":"crossref","unstructured":"Zschenker O, Jung N, Rethmeier J, Trautwein S, Hertel S, Zeigler M, and Ameis D.Characterization of lysosomal acid lipase mutations in the signal peptide and mature polypeptide region causing Wolman disease.J Lipid Res42: 1033\u20131040, 2001.","DOI":"10.1016\/S0022-2275(20)31591-1"}],"container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpregu.00089.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,12]],"date-time":"2021-07-12T22:09:36Z","timestamp":1626127776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpregu.00089.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,11]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2005,11]]}},"alternative-id":["10.1152\/ajpregu.00089.2005"],"URL":"https:\/\/doi.org\/10.1152\/ajpregu.00089.2005","relation":{},"ISSN":["0363-6119","1522-1490"],"issn-type":[{"value":"0363-6119","type":"print"},{"value":"1522-1490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,11]]}}}