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BH~4~ (tetrahydrobiopterin)‐dependent activation, but not the expression, of inducible NOS (nitric oxide synthase)‐2 in proinflammatory cytokine‐stimulated, cultured normal human astrocytes is mediated by MEK–ERK kinases by Anna Chiarini; Ilaria Dal Pra; Rossella Gottardo; Federica Bortolotti; James F. Whitfield; Ubaldo Armato is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

What is BH~4~ (tetrahydrobiopterin)‐dependent activation, but not the expression, of inducible NOS (nitric oxide synthase)‐2 in proinflammatory cytokine‐stimulated, cultured normal human astrocytes is mediated by MEK–ERK kinases about?

## Abstract Nitric oxide (NO) from astrocytes is one of the signalers used by the brain's extensive glial‐neuronal‐vascular network, but its excessive production by pro‐inflammatory cytokine‐stimulated glial cells can be cytodestructive. Here, we show how three pro‐inflammatory cytokines (IL‐1β, TNF‐α, and IFN‐γ) together stimulated the activation, but not the prior expression, of NOS‐2 protein via a mechanism involving MEK–ERKs protein kinases in astrocytes from adult human cerebral temporal cortex. The cytokines triggered a transient burst of p38 MAPK activity and the production of NOS‐2 mRNA which were followed by bursts of MEK–ERK activities, synthesis of the NOS‐2 co‐factor tetrahydrobiopterin (BH~4~), a build‐up of NOS‐2 protein and from it active NOS‐2 enzyme. Selectively inhibiting MEK1/MEK2, but not the earlier burst of p38 MAPK activity, with a brief exposure to U0126 between 24 and 24.5 h after adding the cytokine triad affected neither NOS‐2 expression nor NOS‐2 protein accumulation but stopped BH~4~ synthesis and the assembly of the NOS‐2 protein into active NOS‐2 enzyme. The complete blockage of active NOS‐2 production by the brief exposure to U0126 was bypassed by si

Who reads BH~4~ (tetrahydrobiopterin)‐dependent activation, but not the expression, of inducible NOS (nitric oxide synthase)‐2 in proinflammatory cytokine‐stimulated, cultured normal human astrocytes is mediated by MEK–ERK kinases?

Author

Anna Chiarini; Ilaria Dal Pra; Rossella Gottardo; Federica Bortolotti; James F. Whitfield; Ubaldo Armato

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley (ISSN 0730-2312)

Published

2004

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)