|Dombrink Kurtzman, Mary Ann|
Submitted to: Biochemistry and Molecular Biology Abstracts
Publication Type: Abstract Only
Publication Acceptance Date: 5/20/1999
Publication Date: N/A
Citation: Interpretive Summary:
Technical Abstract: The fungal toxin, fumonisin B1, is a potent ceramide synthase inhibitor, both in vivo and in vitro, in a wide variety of cells. Prior studies with peripheral blood lymphocytes have reported that fumonisin B1 is capable of inhibition of proliferation and induction of apoptosis. In this study, we show that fumonisin B1 (10-100 ug/ml) significantly enhanced nitric oxide production by both resident untreated and LPS-activated rat peritoneal macrophages, and also decreased their viability. In addition, fumonisin B1 did not significantly alter proliferation of untreated or mitogen-induced splenic lymphocytes. The use of the inducible nitric oxide synthase (iNOS) inhibitor NG-monomethyl-L-arginine significantly potentiated the fumonisin B1-mediated splenic T cell proliferative response, thus indicating that nitric oxide was associated with abrogating the effects of fumonisin B1 on lymphocyte proliferation. This represents the first report of nitric oxide production induced by fumonisin B1 in the absence of LPS, and its influence in suppressing fumonisin B1-induced lymphocyte proliferation, and should be considered a previously unrecognized effect of fumonisin exposure.