{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T09:28:11Z","timestamp":1749461291650,"version":"3.40.5"},"reference-count":22,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neonatology"],"published-print":{"date-parts":[[2017]]},"abstract":"<b><i>Background:<\/i><\/b> Severe hemolytic disease of the newborn leads to the release of pro-oxidative free heme (FH). Heme oxygenase (HO) is primarily responsible for detoxifying FH. <b><i>Objective:<\/i><\/b> To investigate the protective effects of HO in a model of heme overload. <b><i>Methods:<\/i><\/b> For in vitro studies, NIH3T3 HO-1-<i>luc<\/i> cells were incubated with 10, 30, or 60 \u00b5<smlcap>M<\/smlcap> FH or methemalbumin (MHA). HO-1 promoter activity was assessed 3, 6, and 24 h after treatment. Cell survival was indexed by viability assays. For in vivo studies, 1- and 5-week-old wild-type (Wt) or HO-1-heterozygous (Het, HO-1<sup>+\/-<\/sup>) mice were given 60 \u00b5mol FH or MHA\/kg intraperitoneally. After 24 h, plasma aspartate aminotransferease (AST)\/alanine transaminase (ALT) and hemopexin, liver HO activity, and lipid peroxidation (LP) were determined. <b><i>Results: <\/i><\/b>In HO-1-<i>luc<\/i> cells, HO-1 promoter activity peaked 6 h after incubation with 30 \u00b5<smlcap>M<\/smlcap> FH (1.6-fold) or 60 \u00b5<smlcap>M<\/smlcap> MHA (2.1-fold) over baseline. Twenty-four hours after exposure to 60 \u00b5<smlcap>M<\/smlcap> FH, a decrease in viability of 80% was found, compared with no decrease after exposure to 60 \u00b5<smlcap>M<\/smlcap> MHA. In 1-week-old Wt and HO-1 Het pups given 60 \u00b5mol FH\/kg, HO activity significantly increased 3.5- and 3.1-fold, respectively. No changes in LP or AST\/ALT levels were observed. In adult Wt and HO-1 Het mice, HO activity increased (3.0- and 2.6-fold, respectively). LP and AST levels significantly increased 28.4- and 2.7-fold, respectively, in adult HO-1 Het mice.<b> <\/b>Hemopexin levels at baseline were higher in adults compared with newborns for both Wt and Het mice. In addition, FH induced hemopexin levels in both adults and newborns, but to a lesser degree in newborns. <b><i>Conclusions:<\/i><\/b> FH is highly toxic in vitro, but its toxicity is abolished when bound to albumin. Newborns appear to be protected from the pro-oxidative effects of FH, which may be mediated by heme binding and a higher absolute HO activity at baseline and after FH-mediated induction.<\/jats:p>","DOI":"10.1159\/000479493","type":"journal-article","created":{"date-parts":[[2017,9,19]],"date-time":"2017-09-19T21:02:17Z","timestamp":1505854937000},"page":"376-383","source":"Crossref","is-referenced-by-count":6,"title":["Heme Oxygenase Activity and Heme Binding in a Neonatal Mouse Model"],"prefix":"10.1159","volume":"112","author":[{"given":"Stephanie","family":"Kourula","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joyce","family":"Ang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flora","family":"Kalish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Vandenabeele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl G.","family":"Sylvester","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1205-6936","authenticated-orcid":false,"given":"Ronald J.","family":"Wong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David K.","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2017,9,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001118"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00115"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-03-272138"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.13.3693"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2787"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1126\/science.337492"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.071130"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1203\/PDR.0b013e31822e1675"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1203\/01.pdr.0000215088.71481.a6"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(88)90006-1"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1038\/jp.2010.173"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.01.050"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-002-0375-x"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.07.012"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2015.22"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-76-12-1057"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1038\/13294"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000000689"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00363.2012"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2768365"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2045"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2010.12.055"}],"container-title":["Neonatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/479493","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/479493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:45:41Z","timestamp":1745426741000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000479493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"references-count":22,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2017,11,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000479493","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.5418928","asserted-by":"subject"}]},"ISSN":["1661-7800","1661-7819"],"issn-type":[{"type":"print","value":"1661-7800"},{"type":"electronic","value":"1661-7819"}],"subject":[],"published":{"date-parts":[[2017]]}}}