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Role of MAP kinase cascades in inducing arginine transporters and nitric oxide synthetase in RAW264 macrophages
Author(s) -
Caivano Matilde
Publication year - 1998
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(98)00578-x
Subject(s) - nitric oxide , lipopolysaccharide , p38 mitogen activated protein kinases , nitric oxide synthase , arginine , chemistry , mapk/erk pathway , interferon gamma , biochemistry , microbiology and biotechnology , kinase , amino acid , biology , in vitro , immunology , organic chemistry
Bacterial lipopolysaccharide (LPS) in the presence of interferon gamma (IFNγ) stimulates the synthesis of the cationic amino acid transporter 2B (CAT‐2B) and inducible nitric oxide synthetase (iNOS) in RAW264 macrophages, which are thought to underlie the increased rate of arginine uptake into these cells and its conversion to nitric oxide, respectively. Here I demonstrate that the LPS‐ and IFNγ‐induced increase in arginine uptake into RAW264 cells is partially suppressed in the presence of PD 98059, partially suppressed in the presence of SB 203580, and completely inhibited by both drugs. In contrast, the LPS‐ and IFNγ‐induced synthesis of CAT‐2B mRNA and iNOS protein is unaffected by PD 98059 and SB 203580. The results indicate that the MAPK/ERK and SAPK2/p38 cascades are both rate‐limiting for LPS‐ and IFNγ‐stimulated arginine uptake, but not for iNOS synthesis. They also suggest that PD 98059 and SB 203580 suppress CAT‐2B synthesis at a post‐transcriptional level.