Alteration of kinase-mediated signalings in murine peritoneal macrophages by aflatoxin B(1).
Aflatoxin B(1) (AFB(1)) is a potent hepatocarcinogen which is thought to exhibit an impairment of specific and non-specific immunity. Macrophages are responsible for non-specific immunity in host defense against tumors and microorganisms, and release a number of cytotoxic compounds, including nitric oxide (NO). We investigate whether the effect of AFB(1) on signal transduction is related to the decrease of NO production in murine peritoneal macrophages. When macrophages were stimulated with lipopolysaccharide (LPS) after AFB(1)-pretreatment, AFB1 decreased the NO production. The percentage of NO production in AFB(1)-pretreated macrophages was inversely increased by the addition of cholera toxin, phorbol 12-myrisate 13-acetate (PMA) and ionomycin. This suggests that AFB(1) affects the function of signaling constituents, including guanine nucleotide-binding protein (G protein), protein kinase C (PKC) and the calcium ion. AFB(1)-pretreatment significantly decreased PKC activity and tyrosine phosphorylation after LPS-stimulation. Taken together, these data propose that the inhibition of LPS-stimulated NO production by AFB(1) is related to the suppression of kinase-mediated intracellular signal transduction in murine peritoneal macrophages.
Moon
E Y
EY
Central Research Laboratories, Dong-Wha Pharm. Ind. Co. Ltd., Anyang-Dong Anyang City, Kyunggido, South Korea.
Rhee
D K
DK
Pyo
S
S
D016604:Aflatoxin B1 / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002273:Carcinogens; D002772:Cholera Toxin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007477:Ions; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000201:enzymology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D010770:Phosphotransferases / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D007476:Ionophores; D007477:Ions; D008070:Lipopolysaccharides; D009569:Nitric Oxide; D015759:Ionomycin; D002772:Cholera Toxin; D016604:Aflatoxin B1; D010770:Phosphotransferases; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium