Herbimycin A suppresses NF-kappa B activation and tyrosine phosphorylation of JAK2 and the subsequent induction of nitric oxide synthase in C6 glioma cells.
Herbimycin A, a potent tyrosine kinase inhibitor, suppressed nitric oxide synthase (NOS) induced by lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma) in C6 glial cells. LPS activated NF-kappa B, and this effect was inhibited by pretreatment with herbimycin A. In addition, IFN-gamma activated the tyrosine protein kinase, JAK2, and tyrosine-phosphorylation by itself was also inhibited by herbimycin A. These results suggest that herbimycin A suppresses iNOS induction by inhibition of both NF-kappa B activation caused by LPS, and tyrosine-phosphorylation of JAK2 caused by IFN-gamma in C6 glioma cells.
Nishiya
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Uehara
T
T
Nomura
Y
Y
D000818:Animals; D001483:Base Sequence; D016227:Benzoquinones; D004789:Enzyme Activation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005910:Glioma; D007371:Interferon-gamma / Q000494:pharmacology; D053614:Janus Kinase 2; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides / Q000494:pharmacology; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D017828:Rifabutin / Q000031:analogs & derivatives; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D047029:Lactams, Macrocyclic; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D011809:Quinones; D017828:Rifabutin; D014443:Tyrosine; C020754:herbimycin; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D011505:Protein-Tyrosine Kinases; C507927:Jak2 protein, rat; D053614:Janus Kinase 2