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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Interactions between the NO-Citrulline Cycle and Brain-derived Neurotrophic Factor in Differentiation of Neural Stem Cells

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Author(s):
Lameu, Claudiana [1] ; Trujillo, Cleber A. [1] ; Schwindt, Telma T. [1] ; Negraes, Priscilla D. [1] ; Pillat, Micheli M. [1] ; Morais, Katia L. P. [2] ; Lebrun, Ivo [2] ; Ulrich, Henning [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508900 Sao Paulo - Brazil
[2] Inst Butantan, Lab Bioquim & Biofis, BR-05503900 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Biological Chemistry; v. 287, n. 35, p. 29690-29701, AUG 24 2012.
Web of Science Citations: 18
Abstract

The diffusible messenger NO plays multiple roles in neuroprotection, neurodegeneration, and brain plasticity. Argininosuccinate synthase (AS) is a ubiquitous enzyme in mammals and the key enzyme of the NO-citrulline cycle, because it provides the substrate L-arginine for subsequent NO synthesis by inducible, endothelial, and neuronal NO synthase (NOS). Here, we provide evidence for the participation of AS and of the NO-citrulline cycle in the progress of differentiation of neural stem cells (NSC) into neurons, astrocytes, and oligodendrocytes. AS expression and activity and neuronal NOS expression, as well as L-arginine and NOx production, increased along neural differentiation, whereas endothelial NOS expression was augmented in conditions of chronic NOS inhibition during differentiation, indicating that this NOS isoform is amenable to modulation by extracellular cues. AS and NOS inhibition caused a delay in the progress of neural differentiation, as suggested by the decreased percentage of terminally differentiated cells. On the other hand, BDNF reversed the delay of neural differentiation of NSC caused by inhibition of NOx production. Alikely cause is the lack of NO, which up-regulated p75 neurotrophin receptor expression, a receptor required for BDNF-induced differentiation of NSC. We conclude that the NO-citrulline cycle acts together with BDNF for maintaining the progress of neural differentiation. (AU)

FAPESP's process: 06/61285-9 - Molecular basis of differentiation of stem and neural progenitor cells
Grantee:Alexander Henning Ulrich
Support Opportunities: Research Projects - Thematic Grants