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Titolo:
Relationship between dopamine-stimulated phospholipid methylation and the single-carbon folate pathway
Autore:
Zhao, R; Chen, Y; Tan, WB; Waly, M; Sharma, A; Stover, P; Rosowsky, A; Malewicz, B; Deth, RC;
Indirizzi:
Northeastern Univ, Dept Pharmaceut Sci, Boston, MA 02115 USA Northeastern Univ Boston MA USA 02115 harmaceut Sci, Boston, MA 02115 USA Cornell Univ, Dept Nutr Sci, Ithaca, NY USA Cornell Univ Ithaca NY USACornell Univ, Dept Nutr Sci, Ithaca, NY USA Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA HarvardUniv Boston MA USA 02115 a Farber Canc Inst, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA Harvard Univ Boston MA USA 02115 em & Mol Pharmacol, Boston, MA 02115 USA Univ Minnesota, Hormel Inst, LIPIDNMR Lab, Austin, MN 55912 USA Univ Minnesota Austin MN USA 55912 st, LIPIDNMR Lab, Austin, MN 55912 USA
Titolo Testata:
JOURNAL OF NEUROCHEMISTRY
fascicolo: 4, volume: 78, anno: 2001,
pagine: 788 - 796
SICI:
0022-3042(200108)78:4<788:RBDPMA>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
5-FORMYLTETRAHYDROFOLATE POLYGLUTAMATES; RECEPTOR; LEUCOVORIN; METABOLISM; ACID;
Keywords:
D4 dopamine receptors; folic acid metabolism; 5-methyltetrahydrofolate; phospholipid methylation; purine metabolism; schizophrenia;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
23
Recensione:
Indirizzi per estratti:
Indirizzo: Deth, RC Northeastern Univ, Dept Pharmaceut Sci, 312 Mugar Hall,360 Huntington Ave,Boston, MA 02115 USA Northeastern Univ 312 Mugar Hall,360 Huntington Ave Boston MA USA 02115
Citazione:
R. Zhao et al., "Relationship between dopamine-stimulated phospholipid methylation and the single-carbon folate pathway", J NEUROCHEM, 78(4), 2001, pp. 788-796

Abstract

In a previous study we demonstrated the ability of dopamine (DA) to stimulate phospholipid methylation (PLM) via a novel mechanism involving the D4 dopamine receptor (D4R) In which single-carbon folates appeared to be the primary source of methyl groups. To further understand the relationship between D4R-mediated PLM and folate metabolism, we examined the effect of several folate pathway interventions on the level of basal and DA-stimulated incorporation of [C-14]-labeled formate, Into phospholipids in cultured SH-SY5Yneuroblastoma cells. These Interventions included: (i) Overexpression of methenyltetrahydrofolate synthetase (MTHFS). (ii) Treatment with 5-formylTHF. (iii) Treatment with the MTHFS inhibitor 5-formyltetrahydrohomofolic acid(5-formylTHHF). (iv) Growth in nucleoside-free media. P-31-NMR was also used to follow DA-induced changes in cell phospholipid composition. MTHFS overexpression and 5-formylTHHF treatment, both of which lower 5-methylTHF levels, each reduced basal PLM and its stimulation by DA. In contrast, 5-formylTHF, which increases 5-methylTHF, caused a dose-dependent increase in bothbasal and DA-stimulated PLM. Growth in nucleoside-free media caused time-dependent changes in PLM, which were due to the absence of purine nucleosides. While basal PLM was maintained at a reduced level, DA-stimulated PLM wasinitially increased followed by a later decrease. Together, these findingsindicate a close functional relationship between single-carbon folate metabolism and DA-stimulated PLM, consistent with a role for 5-methylTHF as themethyl donor for the D4R-mediated process.

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Documento generato il 19/01/20 alle ore 06:14:43