RT info:eu-repo/semantics/article
T1 Peroxynitrite Stimulates L-Arginine Transport System y+ in Glial Cells A POTENTIAL MECHANISM FOR REPLENISHING NEURONAL L-ARGININE
A1 Vega-Agapito, Victoria
A1 Almeida, Angeles
A1 Hatzoglou, Maria
A1 Bolaños, Juan P
AB We have reported previously that peroxynitrite stimulates L-arginine release from astrocytes, but the mechanism responsible for such an effect remains elusive. Toexplore this issue, we studied the regulation ofL-[3H]arginine transport by either exogenous or endogenous peroxynitrite in glial cells. A 2-fold peroxynitritemediated stimulation of L-arginine release in C6 cellswas found to be Na -independent, was prevented by 5mM 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 wastrans-stimulated by 10 mM L-arginine and was inhibitedin a dose-dependent fashion (ki of  40 M) by the systemy  inhibitor N-ethylmaleimide in C6 cells. Endogenousproduction of peroxynitrite in lipopolysaccharidetreated astrocytes triggered an increased L-argininetransport activity without affecting Cat1 L-argininetransporter mRNA levels. However, Western blot analyses of peroxynitrite-treated astrocytes and C6 glial cellsrevealed a 3-nitrotyrosinated anti-Cat1-immunopositiveband, strongly suggesting peroxynitrite-mediated Cat1nitration. 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 releasedfrom astrocytes was efficiently taken up by neurons inan insert-based co-culture system. These resultsstrongly suggest that peroxynitrite-mediated activationof the Cat1 transporter in glial cells may serve as amechanism focused to replenish L-arginine in the neighboring neurons.
PB y The American Society for Biochemistry and Molecular Biology, Inc
YR 2002
FD 2002-08-16
LK https://uvadoc.uva.es/handle/10324/65608
UL https://uvadoc.uva.es/handle/10324/65608
LA eng
NO The Journal of Biolgical Chemistry, agosto 16, 277, 33, 29753-29759
NO Producción Científica
DS UVaDOC
RD 17-jul-2024