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oai:uvadoc.uva.es:10324/656082025-09-10T12:18:16Zcom_10324_1145com_10324_931com_10324_894col_10324_1254

Peroxynitrite Stimulates L-Arginine Transport System y+ in Glial Cells A POTENTIAL MECHANISM FOR REPLENISHING NEURONAL L-ARGININE Vega Agapito, María Victoria Almeida, Angeles Hatzoglou, Maria Bolaños, Juan P Producción Científica We have reported previously that peroxynitrite stimulates L-arginine release from astrocytes, but the mechanism responsible for such an effect remains elusive. To explore this issue, we studied the regulation of L-[3 H]arginine transport by either exogenous or endogenous peroxynitrite in glial cells. A 2-fold peroxynitritemediated stimulation of L-arginine release in C6 cells was found to be Na -independent, was prevented by 5 mM L-arginine and, although only in the presence of Na , was blocked by 5 mM L-alanine or L-leucine. Peroxynitrite-mediated stimulation of L-arginine uptake was trans-stimulated by 10 mM L-arginine and was inhibited in a dose-dependent fashion (ki of 40 M) by the system y inhibitor N-ethylmaleimide in C6 cells. Endogenous production of peroxynitrite in lipopolysaccharidetreated astrocytes triggered an increased L-arginine transport activity without affecting Cat1 L-arginine transporter mRNA levels. However, Western blot analyses of peroxynitrite-treated astrocytes and C6 glial cells revealed a 3-nitrotyrosinated anti-Cat1-immunopositive band, strongly suggesting peroxynitrite-mediated Cat1 nitration. Furthermore, peroxynitrite stimulation of Larginine release was abolished in fibroblast cells homozygous for a targeted inactivation of the Cat1 gene. Finally, peroxynitrite-triggered L-arginine released from astrocytes was efficiently taken up by neurons in an insert-based co-culture system. These results strongly suggest that peroxynitrite-mediated activation of the Cat1 transporter in glial cells may serve as a mechanism focused to replenish L-arginine in the neighboring neurons. 2024-02-02T23:14:37Z 2024-02-02T23:14:37Z 2002 info:eu-repo/semantics/article The Journal of Biolgical Chemistry, agosto 16, 277, 33, 29753-29759 https://uvadoc.uva.es/handle/10324/65608 10.1074/jbc.M203728200 29753 33 29759 277 eng https://www.jbc.org/action/showPdf?pii=S0021-9258%2818%2975638-X info:eu-repo/semantics/openAccess y The American Society for Biochemistry and Molecular Biology, Inc SI