{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:06:40Z","timestamp":1791176800689,"version":"4.1.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"6","funder":[{"DOI":"10.13039\/100000071","name":"HHS | NIH | National Institute of Child Health and Human Development (NICHD)","doi-asserted-by":"publisher","award":["HD-017644"],"award-info":[{"award-number":["HD-017644"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"HHS | NIH | National Institute of Child Health and Human Development (NICHD)","doi-asserted-by":"publisher","award":["HD-047584"],"award-info":[{"award-number":["HD-047584"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL-51952"],"award-info":[{"award-number":["HL-51952"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL-091797"],"award-info":[{"award-number":["HL-091797"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences (NIGMS)","doi-asserted-by":"publisher","award":["GN-102773"],"award-info":[{"award-number":["GN-102773"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Renal Physiology"],"published-print":{"date-parts":[[2015,3,15]]},"abstract":"<jats:p>\n                    Angiotensin 1\u20137 [ANG-(1\u20137)] is expressed within the kidney and exhibits renoprotective actions that antagonize the inflammatory, fibrotic, and pro-oxidant effects of ANG II. We previously identified an peptidase that preferentially metabolized ANG-(1\u20137) to ANG-(1\u20134) in the brain medulla and cerebrospinal fluid (CSF) of sheep (Marshall AC, Pirro NT, Rose JC, Diz DI, Chappell MC. J Neurochem 130: 313\u2013323, 2014); thus the present study established the expression of the peptidase in the kidney. Utilizing a sensitive HPLC-based approach, we demonstrate a peptidase activity that hydrolyzed ANG-(1\u20137) to ANG-(1\u20134) in the sheep cortex, isolated tubules, and human HK-2 renal epithelial cells. The peptidase was markedly sensitive to the metallopeptidase inhibitor JMV-390; human HK-2 cells expressed subnanomolar sensitivity (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.5 nM) and the highest specific activity (123 \u00b1 5 fmol\u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7mg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) compared with the tubules (96 \u00b1 12 fmol\u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7mg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) and cortex (107 \u00b1 9 fmol\u00b7min\n                    <jats:sup>\u22121<\/jats:sup>\n                    \u00b7mg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ). The peptidase was purified 41-fold from HK-2 cells; the activity was sensitive to JMV-390, the chelator o-phenanthroline, and the mercury-containing compound p-chloromercuribenzoic acid (PCMB), but not to selective inhibitors against neprilysin, neurolysin and thimet oligopeptidase. Both ANG-(1\u20137) and its endogenous analog [Ala\n                    <jats:sup>1<\/jats:sup>\n                    ]-ANG-(1\u20137) (alamandine) were preferentially hydrolyzed by the peptidase compared with ANG II, [Asp\n                    <jats:sup>1<\/jats:sup>\n                    ]-ANG II, ANG I, and ANG-(1\u201312). Although the ANG-(1\u20137) peptidase and insulin-degrading enzyme (IDE) share similar inhibitor characteristics of a metallothiolendopeptidase, we demonstrate marked differences in substrate specificity, which suggest these peptidases are distinct. We conclude that an ANG-(1\u20137) peptidase is expressed within the renal proximal tubule and may play a potential role in the renal renin-angiotensin system to regulate ANG-(1\u20137) tone.\n                  <\/jats:p>","DOI":"10.1152\/ajprenal.00609.2014","type":"journal-article","created":{"date-parts":[[2015,1,8]],"date-time":"2015-01-08T02:16:50Z","timestamp":1420683410000},"page":"F594-F601","source":"Crossref","is-referenced-by-count":18,"title":["An angiotensin-(1\u20137) peptidase in the kidney cortex, proximal tubules, and human HK-2 epithelial cells that is distinct from insulin-degrading enzyme"],"prefix":"10.1152","volume":"308","author":[{"given":"Bryan A.","family":"Wilson","sequence":"first","affiliation":[{"name":"Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Cartolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nildris","family":"Cruz-Diaz","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Cartolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyson C.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Cartolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy T.","family":"Pirro","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Cartolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixin","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Cartolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"TanYa M.","family":"Gwathmey","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Cartolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James C.","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Wake Forest University School of Medicine, Winston-Salem, North Cartolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark C.","family":"Chappell","sequence":"additional","affiliation":[{"name":"Hypertension and Vascular Research Center, Wake Forest University School of Medicine, Winston-Salem, North Cartolina; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.193"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2014.09.010"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-012-1120-0"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006170200"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2008.03782.x"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1139\/y06-002"},{"key":"B7","doi-asserted-by":"crossref","first-page":"2733","DOI":"10.1002\/cphy.c120002","volume":"2","author":"Chappell MC","year":"2012","journal-title":"Compr Physiol"},{"key":"B8","doi-asserted-by":"crossref","first-page":"16518","DOI":"10.1016\/S0021-9258(19)84737-3","volume":"264","author":"Chappell MC","year":"1989","journal-title":"J Biol Chem"},{"key":"B9","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3389\/fendo.2013.00201","volume":"4","author":"Chappell MC","year":"2014","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1021\/bi8016125"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00493.2011"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00487.2011"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2002.kid559.x"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00525.2011"},{"key":"B15","first-page":"200","volume":"14","author":"Kitabgi P","year":"1993","journal-title":"Neursoci Lett"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120089"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301077"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature13297"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1021\/bi801192h"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12720"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00321.2013"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2013.12.006"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1991.tb16374.x"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.163519"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2011.01.009"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00317.2005"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1021\/bi960582q"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01274"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1159\/000318176"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00139.2006"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.2337\/diab.35.6.675"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1159\/000320593"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00177.2014"},{"key":"B34","author":"Zhang K","journal-title":"Kidney Int"}],"container-title":["American Journal of Physiology-Renal Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajprenal.00609.2014","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T06:19:05Z","timestamp":1650953945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajprenal.00609.2014"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,15]]},"references-count":34,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2015,3,15]]}},"alternative-id":["10.1152\/ajprenal.00609.2014"],"URL":"https:\/\/doi.org\/10.1152\/ajprenal.00609.2014","relation":{},"ISSN":["1931-857X","1522-1466"],"issn-type":[{"value":"1931-857X","type":"print"},{"value":"1522-1466","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,15]]}}}