{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:33:12Z","timestamp":1790051592893,"version":"4.0.1"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,3,25]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Studies with Wilson disease model mice that accumulate excessive copper, due to a dysfunctional ATP7B \u201ccopper pump\u201d resulting in decreased biliary excretion, showed that the compensatory increase in urinary copper loss was due to a small copper carrier (\u223c1\u00a0kDa) (SCC). We show here that SCC is also present in the blood plasma of normal and Wilson disease model mice and dogs, as determined by ultrafiltration and size exclusion chromatography (SEC). It is secreted by cultured hepatic and enterocytic cells, as determined by pretreatment with 67Cu nitrilotriacetate (NTA) or nonradioactive 5\u201310\u00a0\u03bcM Cu-NTA, and collecting and examining 3\u00a0kDa ultrafiltrates of the conditioned media, where a single major copper peak is detected by SEC. Four different cultured cell types exposed to the radiolabeled SCC all took up the 67Cu at various rates. Rates differed somewhat when uptake was from Cu-NTA. Uptake of SCC-67Cu was inhibited by excess nonradioactive Cu(I) or Ag(I) ions, suggesting competition for uptake by copper transporter 1 (CTR1). Knockout of CTR1 in fibroblasts reduced uptake rates by 60%, confirming its participation, but also involvement of other transporters. Inhibitors of endocytosis, or an excess of metal ions taken up by divalent metal transporter 1, did not decrease SCC-67Cu uptake. The results imply that SCC may play a significant role in copper transport and homeostasis, transferring copper particularly from the liver (but also intestinal cells) to other cells within the mammalian organism, as well as spilling excess into the urine in copper overload\u2014as an alternative means of copper excretion.<\/jats:p>","DOI":"10.1093\/mtomcs\/mfac006","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T20:15:03Z","timestamp":1645560903000},"source":"Crossref","is-referenced-by-count":23,"title":["Secretion and uptake of copper via a small copper carrier in blood fluid"],"prefix":"10.1093","volume":"14","author":[{"given":"B D","family":"Gioilli","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, 800\u00a0N State College Blvd., Fullerton, CA 92834-6866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T Z","family":"Kidane","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, 800\u00a0N State College Blvd., Fullerton, CA 92834-6866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Fieten","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University , 3584 CM Utrecht, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Tellez","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, 800\u00a0N State College Blvd., Fullerton, CA 92834-6866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Dalphin","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, 800\u00a0N State College Blvd., Fullerton, CA 92834-6866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, 800\u00a0N State College Blvd., Fullerton, CA 92834-6866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, 800\u00a0N State College Blvd., Fullerton, CA 92834-6866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3937-9268","authenticated-orcid":false,"given":"M C","family":"Linder","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, California State University, 800\u00a0N State College Blvd., Fullerton, CA 92834-6866, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,2,24]]},"reference":[{"key":"2024020308284832800_bib1","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4757-9432-8","article-title":"Biochemistry of copper","volume-title":"Biochemistry of the Elements","author":"Linder","year":"1991"},{"issue":"5","key":"2024020308284832800_bib2","doi-asserted-by":"crossref","first-page":"7972S","DOI":"10.1093\/ajcn\/63.5.797","article-title":"Copper biochemistry and molecular biology","volume":"63","author":"Linder","year":"1996","journal-title":"Am. 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