{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:49:23Z","timestamp":1788511763420,"version":"build-2803163510"},"reference-count":75,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T00:00:00Z","timestamp":1628640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1-NS-065201"],"award-info":[{"award-number":["RO1-NS-065201"]}],"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":["5RO1-NS-065201-02S1"],"award-info":[{"award-number":["5RO1-NS-065201-02S1"]}],"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":["R15-NS-116478"],"award-info":[{"award-number":["R15-NS-116478"]}],"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":["3R15-NS116478-01S1"],"award-info":[{"award-number":["3R15-NS116478-01S1"]}],"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":["R25GM110513"],"award-info":[{"award-number":["R25GM110513"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Polyamines (PAs) are polycationic biomolecules containing multiple amino groups. Patients with HIV-associated neurocognitive disorder (HAND) have high concentrations of the polyamine N-acetylated spermine in their brain and cerebral spinal fluid (CSF) and have increased PA release from astrocytes. These effects are due to the exposure to HIV-Tat. In healthy adult brain, PAs are accumulated but not synthesized in astrocytes, suggesting that PAs must enter astrocytes to be N-acetylated and released. Therefore, we tested if Cx43 hemichannels (Cx43-HCs) are pathways for PA flux in control and HIV-Tat-treated astrocytes. We used biotinylated spermine (b-SPM) to examine polyamine uptake. We found that control astrocytes and those treated with siRNA-Cx43 took up b-SPM, similarly suggesting that PA uptake is via a transporter\/channel other than Cx43-HCs. Surprisingly, astrocytes pretreated with both HIV-Tat and siRNA-Cx43 showed increased accumulation of b-SPM. Using a novel polyamine transport inhibitor (PTI), trimer 44NMe, we blocked b-SPM uptake, showing that PA uptake is via a PTI-sensitive transport mechanism such as organic cation transporter. Our data suggest that Cx43 HCs are not a major pathway for b-SPM uptake in the condition of normal extracellular calcium concentration but may be involved in the release of PAs to the extracellular space during viral infection.<\/jats:p>","DOI":"10.3390\/biom11081187","type":"journal-article","created":{"date-parts":[[2021,8,11]],"date-time":"2021-08-11T21:48:12Z","timestamp":1628718492000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Uptake of Biotinylated Spermine in Astrocytes: Effect of Cx43 siRNA, HIV-Tat Protein and Polyamine Transport Inhibitor on Polyamine Uptake"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6778-408X","authenticated-orcid":false,"given":"Christian J.","family":"Malpica-Nieves","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Central University of the Caribbean, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yomarie","family":"Rivera","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Central University of the Caribbean, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David E.","family":"Rivera-Aponte","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Central University of the Caribbean, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7101-1311","authenticated-orcid":false,"given":"Otto","family":"Phanstiel","sequence":"additional","affiliation":[{"name":"Department of Medical Education, University of Central Florida, Orlando, FL 32816, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6253-9808","authenticated-orcid":false,"given":"R\u00fcdiger W.","family":"Veh","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Zell- und Neurobiologie, Charit\u00e9, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misty J.","family":"Eaton","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Central University of the Caribbean, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Serguei N.","family":"Skatchkov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Central University of the Caribbean, Bayamon, PR 00956, USA"},{"name":"Department of Physiology, Central University of the Caribbean, Bayamon, PR 00956, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/S0092-8674(02)00639-6","article-title":"Origins of Human Virus Diversity","volume":"108","author":"Sharp","year":"2002","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/sim.1342","article-title":"Comparison of HIV-1 and HIV-2 infectivity from a prospective cohort study in Senegal","volume":"22","author":"Gilbert","year":"2003","journal-title":"Stat. 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