Role of MAP kinase activation in Nramp1 mRNA stability in RAW264.7 macrophages expressing Nramp1(Gly169).
Nramp1 (natural resistance-associated macrophage protein 1) is a phagosomal iron transport molecule. In addition to its anti-microbial activity, Nramp1 exerts a wide range of pleiotropic effects, including increased stability of Nramp1 mRNA and a variety of other mRNA species. Previously, we showed that the increased stability of Nramp1 mRNA is regulated by an oxidant-generated signaling pathway that requires PKC. In the current study, we show that inhibition of ERK1,2 and p38 MAP kinase activities decreases Nramp1 mRNA stability in Mycobacterium avium infected RAW264.7 cells expressing Nramp1(Gly169) but not in RAW264.7-Nramp1(Asp169) cells. Phosphorylation of ERK1,2 and p38 MAP kinases, which could be inhibited by the anti-oxidant BHA and a protein kinase C inhibitor, was higher in M. avium infected RAW264.7-Nramp1(Gly169) cells than in RAW26.47-Nramp1(Asp169) cells. These results suggest that generation of oxidants by Nramp1 iron transport activates MAP kinase signaling cascades that result in stabilization of Nramp1 mRNA.
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA. lafuse.1@osu.edu
William P
WP
Lafuse
Gail R
GR
Alvarez
Bruce S
BS
Zwilling
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D027682:Cation Transport Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009162:Mycobacterium avium / Q000276:immunology / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D020871:RNA Stability; D017382:Reactive Oxygen Species / Q000378:metabolism; D024483:Vitamin K 3 / Q000494:pharmacology; D000099173:Natural Resistance-associated Macrophage Protein 1
D000975:Antioxidants; D002083:Butylated Hydroxyanisole; D027682:Cation Transport Proteins; D004791:Enzyme Inhibitors; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D017382:Reactive Oxygen Species; D024483:Vitamin K 3; D000099173:Natural Resistance-associated Macrophage Protein 1