{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:45:22Z","timestamp":1786977922171,"version":"build-2736575974"},"reference-count":77,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK\u2010032948"],"award-info":[{"award-number":["DK\u2010032948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["DK\u2010032949"],"award-info":[{"award-number":["DK\u2010032949"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The biosynthesis of many of the peptides involved in homeostatic control requires peptidylglycine \u03b1\u2010amidating monooxygenase (PAM), an ancient, highly conserved copper\u2010 and ascorbate\u2010dependent enzyme. Using the production of amidated chromogranin A to monitor PAM function in tumor cells, physiologically relevant levels of hypoxia were shown to inhibit this monooxygenase. The ability of primary pituitary cells exposed to hypoxic conditions for 4\u2009h to produce amidated chromogranin A was similarly inhibited. The affinity of the purified monooxygenase for oxygen (\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>m<\/jats:sub>\n                    \u2009=\u200999\u2009\u00b1\u200919\u2009\u03bcM) was consistent with this result. The ability of PAM to alter secretory pathway behavior under normoxic conditions required its monooxygenase activity. Under normoxic conditions, hypoxia\u2010inducible factor 1a levels in dense cultures of corticotrope tumor cells expressing high levels of PAM exceeded those in control cells; expression of inactive monooxygenase did not have this effect. The effects of hypoxia on levels of two PAM\u2010regulated genes (activating transcription factor 3 [\n                    <jats:italic>Atf3<\/jats:italic>\n                    ] and FK506 binding protein 2\u00a0[\n                    <jats:italic>Fkbp2<\/jats:italic>\n                    ]) differed in cells expressing high versus low levels of PAM. Putative hypoxia response elements occur in both human and mouse\n                    <jats:italic>PAM<\/jats:italic>\n                    , and\n                    <jats:italic>hPAM<\/jats:italic>\n                    has consistently been identified as one of the genes upregulated in response to hypoxia. Expression of\n                    <jats:italic>PAM<\/jats:italic>\n                    is also known to alter gene expression. A quarter of the genes consistently upregulated in response to hypoxia were downregulated following increased expression of PAM. Taken together, our data suggest roles for PAM and amidated peptide secretion in the coordination of tissue\u2010specific responses to hypoxia.\n                  <\/jats:p>","DOI":"10.1002\/jcp.30457","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T00:52:15Z","timestamp":1622595135000},"page":"7745-7758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Multiple roles for peptidylglycine \u03b1\u2010amidating monooxygenase in the response to hypoxia"],"prefix":"10.1002","volume":"236","author":[{"given":"Vishwanatha K. S.","family":"Rao","sequence":"first","affiliation":[{"name":"Department of Neuroscience University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty A.","family":"Eipper","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Connecticut Health Center Farmington Connecticut USA"},{"name":"Department of Molecular Biology and Biophysics University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1154-1331","authenticated-orcid":false,"given":"Richard E.","family":"Mains","sequence":"additional","affiliation":[{"name":"Department of Neuroscience University of Connecticut Health Center Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.12.3.629"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209781"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mss114"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/tra.12194"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines8010010"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2004410117"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2011.01258.x"},{"issue":"1","key":"e_1_2_9_9_1","first-page":"189","article-title":"Hypoxia\u2010inducible factor\u2010dependent breast cancer\u2010mesenchymal stem cell bidirectional signaling promotes metastasis","volume":"123","author":"Chaturvedi P.","year":"2013","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.144.3.459"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1109085108"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1530\/EC-14-0027"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.6.3.485"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409238.2013.838205"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv-1-1-1"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.16.5144"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)84435-6"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00009a016"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.141.8.7620"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511408200"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi061734c"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi973004y"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00848a005"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705911200"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304982200"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.02-03-0040"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200903066"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1590\/1678-4685-gmb-2016-0324"},{"key":"e_1_2_9_29_1","first-page":"2685","article-title":"Induction of apoptosis by iron depletion in the human breast cancer MCF\u20107 cell line and the 13762NF rat mammary adenocarcinoma in vivo","volume":"22","author":"Jiang X. P.","year":"2004","journal-title":"Anticancer Research"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2006.10.012"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.12386"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvw228"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218320"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7665-2_2"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0260280"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9708747"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(97)79007-4"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.36.23012"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-15-0266"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-019-03065-w"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25728"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22732-9"},{"issue":"5","key":"e_1_2_9_43_1","first-page":"3813","article-title":"Mesenchymal stem cell\u2011derived extracellular vesicles prevent neural stem cell hypoxia injury via promoting miR\u2011210\u20113p expression","volume":"22","author":"Li F.","year":"2020","journal-title":"Molecular Medicine Reports"},{"key":"e_1_2_9_44_1","first-page":"142","article-title":"Dynamic expression changes in the transcriptome of the prefrontal cortex after repeated exposure to cocaine in mice","volume":"8","author":"Li M.","year":"2017","journal-title":"Frontiers in Pharmacology"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M700478-MCP200"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000566"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14249"},{"key":"e_1_2_9_48_1","first-page":"2929","article-title":"Kalirin, a multifunctional PAM COOH\u2010terminal domain interactor protein, affects cytoskeletal organization and ACTH secretion from AtT\u201020 cells","volume":"274","author":"Mains R. E.","year":"1999","journal-title":"Journal of Biocommunication"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00235"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08491-z"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-118-4-1284"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.117.4.717"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.121.1.23"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.29.17526"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2013.06.014"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-020518-114427"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0178011"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1910495116"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1007\/PL00000763"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.4137\/BMI.S8247"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.035782"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.pmbts.2015.12.001"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27528"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.07.006"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.667246"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6750-14-76"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.27467"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.95.2.559"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2013.12.010"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2009"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/ie990577t"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2012.09.016"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1991.260.6.C1131"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1042\/CBI20090154"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00271348"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.2147\/HP.S92198"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.3062005re12"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7169348"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30457","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcp.30457","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.30457","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T05:58:14Z","timestamp":1693288694000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.30457"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6]]},"references-count":77,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1002\/jcp.30457"],"URL":"https:\/\/doi.org\/10.1002\/jcp.30457","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6]]},"assertion":[{"value":"2021-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}