J Korean Neuropsychiatr Assoc.  1999 Jul;38(4):881-893.

Signaling Pathway of the Bacterial Lipopolysaccharide-induced Generation of Nitric Oxide in Rat Primary Astorcytes

Affiliations
  • 1Department of Neuropsychiatry, College of Medicine, Wonkwang University, Iksan, Iksan, Korea.
  • 2Department of Microbiology, College of Medicine, Wonkwang University, Iksan, Korea.

Abstract

OBJECTIVES: Nitric oxide(NO)plays an important role in pathophysiology of stroke and various neurodegenerative diseases. This study is designed to elucidate the mechanisms by which signaling pathway of LPS-stimulated NO generation in rat prmary astrocytes may be mediated by MAP kinase cascades and transcriptional activation of NF-kB. METHOD: The generation of NO from primary rat neonatal astrocytes was measured by using Greese's reagents and Western blot analysis with including Erk, JNK1 and p38 was assessed by in vitro immunecomplex kinase assay. Activation of transcriptional activator, NF-kB, was determined by using electrophoretic mobility shift assay.
RESULTS
Treatment of cultured rat primary neonatal astorcytes with LPS results in the generation of NO as well as increase in the expression of inducible nitric oxide synthase(iNOS) LPS-induced NO generation is inhibited by the addition of inhibitors of MEK and JNK1/SPAK, PD 98059 and curcumin. LPS also imcreases the phosphotransferase activity of Erk as well as JNK1 and increases the phosphorylation of p38. Inhibition of Ras results in decrease of LPS-inudced NO generation. cAMP decreases the LPS-induced NO generation via inhibition of JNK1. Furthermore LPS activates transcriptional activator, NF-kB which is inhibited by the addition of inhibitors of MEK and JNK.
CONCLUSION
These data suggest that MAP kinases, especially Erk and JNK1, may mediate the signaling cascade of LPS-induced NO generation in rat primary astrocytes via activation of transcriptional factor, NF-kB.

Keyword

Signaling pathway; No generation; Astrocyte

MeSH Terms

Animals
Astrocytes
Blotting, Western
Curcumin
Electrophoretic Mobility Shift Assay
Indicators and Reagents
MAP Kinase Signaling System
Neurodegenerative Diseases
NF-kappa B
Nitric Oxide*
Phosphorylation
Phosphotransferases
Rats*
Stroke
Transcriptional Activation
Curcumin
Indicators and Reagents
NF-kappa B
Nitric Oxide
Phosphotransferases
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