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The involvement of polyamine uptake and synthesis pathways in the proliferation of neonatal astrocytes.
Malpica-Nieves, Christian J; Rivera-Aponte, David E; Tejeda-Bayron, Flavia A; Mayor, Angel M; Phanstiel, Otto; Veh, Rüdiger W; Eaton, Misty J; Skatchkov, Serguei N.
Affiliation
  • Malpica-Nieves CJ; Department of Biochemistry, School of Medicine, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
  • Rivera-Aponte DE; Department of Biochemistry, School of Medicine, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
  • Tejeda-Bayron FA; Department of Biochemistry, School of Medicine, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
  • Mayor AM; Department of Internal Medicine, Universidad Central del Caribe, Bayamón, PR, 00956, USA.
  • Phanstiel O; Department of Medical Education, University of Central Florida, Orlando, FL, 32816, USA.
  • Veh RW; Institut für Zell- Und Neurobiologie, Charité, 10117, Berlin, Germany.
  • Eaton MJ; Department of Biochemistry, School of Medicine, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR, 00960-6032, USA.
  • Skatchkov SN; Department of Biochemistry, School of Medicine, Universidad Central del Caribe, P.O. Box 60327, Bayamón, PR, 00960-6032, USA. serguei.skatchkov@uccaribe.edu.
Amino Acids ; 52(8): 1169-1180, 2020 Aug.
Article in En | MEDLINE | ID: mdl-32816168
Polyamines (PAs), such as spermidine (SPD) and spermine (SPM), are essential to promote cell growth, survival, proliferation, and longevity. In the adult central nervous system (CNS), SPD and SPM are accumulated predominantly in healthy adult glial cells where PA synthesis is not present. To date, the accumulation and biosynthesis of PAs in developing astrocytes are not well understood. The purpose of the present study was to determine the contribution of uptake and/or synthesis of PAs using proliferation of neonatal astrocytes as an endpoint. We inhibited synthesis of PAs using α-difluoromethylornithine (DFMO; an inhibitor of the PA biosynthetic enzyme ornithine decarboxylase (ODC)) and inhibited uptake of PAs using trimer44NMe (PTI; a novel polyamine transport inhibitor). DFMO, but not PTI alone, blocked proliferation, suggesting that PA biosynthesis was present. Furthermore, exogenous administration of SPD rescued cell proliferation when PA synthesis was blocked by DFMO. When both synthesis and uptake of PAs were inhibited (DFMO + PTI), exogenous SPD no longer supported proliferation. These data indicate that neonatal astrocytes synthesize sufficient quantities of PAs de novo to support cell proliferation, but are also able to import exogenous PAs. This suggests that the PA uptake mechanism is present in both neonates as well as in adults and can support cell proliferation in neonatal astrocytes when ODC is blocked.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polyamines / Astrocytes Limits: Animals Language: En Journal: Amino Acids Journal subject: BIOQUIMICA Year: 2020 Document type: Article Affiliation country: United States Country of publication: Austria

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Polyamines / Astrocytes Limits: Animals Language: En Journal: Amino Acids Journal subject: BIOQUIMICA Year: 2020 Document type: Article Affiliation country: United States Country of publication: Austria