{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T16:46:45Z","timestamp":1774630005401,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T00:00:00Z","timestamp":1550102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2020,2,14]],"date-time":"2020-02-14T00:00:00Z","timestamp":1581638400000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/rsc.li\/journals-terms-of-use"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81400218"],"award-info":[{"award-number":["81400218"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81230004"],"award-info":[{"award-number":["81230004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81400218"],"award-info":[{"award-number":["81400218"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81230004"],"award-info":[{"award-number":["81230004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rsc.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Myocardial ischemia leads to copper efflux from the heart. The ischemic tissue with a low copper content fails to take up copper from the circulation even under the conditions of serum copper elevation. Cardiac copper repletion thus requires other available forms of this element than those currently known to bind to copper transport proteins. The copper complex of triethylenetetramine (TETA) is a metabolite of TETA, which has the potential to increase cardiac copper content in vivo. In the present study, we synthesized Cu(ii)\u2013TETA, analyzed its crystal structure, and demonstrated the role of this compound in facilitating copper accumulation in primary cultures of neonatal rat cardiomyocytes. The Cu(ii)\u2013TETA compound formed a square pyramidal chloride salt [Cu(TETA)Cl]Cl structure, which dissociates from chloride in aqueous solution to yield the four-coordinate dication Cu(ii)\u2013TETA. Cu(ii)\u2013TETA was accumulated as an intact compound in cardiomyocytes. Analysis from time-dependent copper accumulation in cardiomyocytes defined a different dynamic process in copper uptake between Cu(ii)\u2013TETA and CuCl2 exposure. An additive copper accumulation in cardiomyocytes was found when the cells were exposed to both CuCl2 and Cu(ii)\u2013TETA. Gene silencing of copper transport 1 (CTR1) did not affect cross-membrane transportation of Cu(ii)\u2013TETA, but inhibited copper cellular accumulation from CuCl2. Furthermore, the uptake of Cu(ii)\u2013TETA by cardiomyocytes was ATP-dependent. It is thus concluded that the formation of Cu(ii)\u2013TETA facilitates copper accumulation in cardiomyocytes through an active CTR1-independent transportation process.<\/jats:p>","DOI":"10.1039\/c8mt00277k","type":"journal-article","created":{"date-parts":[[2019,2,14]],"date-time":"2019-02-14T09:25:15Z","timestamp":1550136315000},"page":"565-575","update-policy":"https:\/\/doi.org\/10.1039\/rsc_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Active uptake of hydrophilic copper complex Cu(<scp>ii<\/scp>)\u2013TETA in primary cultures of neonatal rat cardiomyocytes"],"prefix":"10.1093","volume":"11","author":[{"given":"Chunyan","family":"Fu","sequence":"first","affiliation":[{"name":"Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China"},{"name":"Sichuan Regenerative Medicine Engineering and Technology Center, Chengdu, Sichuan 610094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhong","family":"Lizhao","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenghui","family":"Luo","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig A","family":"Grapperhaus","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueqin","family":"Ding","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China"},{"name":"Sichuan Regenerative Medicine Engineering and Technology Center, Chengdu, Sichuan 610094, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8449-7904","authenticated-orcid":false,"given":"Y James","family":"Kang","sequence":"additional","affiliation":[{"name":"Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China"},{"name":"Sichuan Regenerative Medicine Engineering and Technology Center, Chengdu, Sichuan 610094, China"},{"name":"Memphis Institute for Regenerative Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,2,14]]},"reference":[{"key":"2021121516074594000_cit1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/nchembio.72","article-title":"Mechanisms for copper acquisition, distribution and regulation","volume":"4","author":"Kim","year":"2008","journal-title":"Nat. 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James Kang (ORCID)","URL":"http:\/\/orcid.org\/0000-0001-8449-7904","name":"identifier","group":{"name":"author_identifiers","label":"IDENTIFIERS"}},{"value":"Single-blind","order":2,"name":"peer_review_method","group":{"name":"peer_review_method","label":"PEER REVIEW METHOD"}},{"value":"Received 28 September 2018; Accepted 4 February 2019;  Advance Article published 14 February 2019;  Version of Record published 20 March 2019","order":1,"name":"history","group":{"name":"publication_history","label":"PUBLICATION HISTORY"}}]}}