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Title: INTERACTIONS OF FUMONISINS AND SPHINGOID BASES WITH GTP-BINDING PROTEINS

Author
item HO, ANDREW - U OF IL, COLLEGE OF MED
item PENG, RICK - U OF IL, COLLEGE OF MED
item HO, ALLAN - U OF IL, COLLEGE OF MED
item DUFFIELD, ROSE - U OF IL, COLLEGE OF MED
item Dombrink Kurtzman, Mary Ann

Submitted to: Biochemical Archives
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/3/1996
Publication Date: N/A
Citation: N/A

Interpretive Summary: Fumonisins are toxins produced by fungi commonly found on corn worldwide and are associated with certain animal diseases. Because fumonisins have been shown to specifically disrupt cellular metabolism of essential chemicals (sphingolipids), studies were undertaken to examine the interaction of fumonisins and the building blocks of sphingolipids (sphingoid bases) with cellular proteins. Results indicated that there were interactions among fumonisins and sphingoid bases with particular proteins (G proteins), which are located in cellular membranes and are involved in interactions between cells. For scientists, this information predicts at a molecular level what effects fumonisin may have on chemical signaling between cells. For animal growers, these studies provide a means for understanding symptoms following exposure to fungi that produce fumonisins.

Technical Abstract: Fumonisins (FB) and sphingoid bases, sphingosine (So) and sphinganine (Sa), were shown to interact with GTP-binding proteins in rat brain plasma membranes and bovine retina rod outer segments. The effects of FBs differed significantly from the sphingoid bases on [3H]-Gpp(NH)p binding and were found to depend on phosphorylating conditions and Ca2+ in the incubation medium. FB1 produced a concentration-dependent increase in [3H]-Gpp(NH)p binding whereas both Sa and So showed inhibition with an inhibitory concentration of 50% (IC50) of 7.5 x 10-5 M. To mimic the effects of FB1 inhibition of ceramide synthase in vivo leading to increase in the Sa:So ratios, we determined the effects of FB1 and HFB1 on [3H]-Gpp(NH)p binding in the presence of a range of Sa:So ratios (1:1 to 39:1). HFB1, but not FB1, was found to reverse the increase in G protein binding observed with the increases in Sa:So ratios. Both FB1 and HFB1 effects on G protein binding and with the changing Sa:So ratios were abolished under Ca2+-free conditions and in the presence of EGTA (0.45 mM), indicating the effects were Ca2+- dependent. Both FB1 and HFB1 were shown to inhibit GTPase activity of the ROS with IC50 at 1.1 x 10-4 M and 1.2 X 10-4 M, respectively, whereas Sa and So alone produced only 23% and 21.3% inhibition at 10-4 M, respectively. However, in the presence of HFB1 (10-4 M), instead of additive effects, the inhibition observed with Sa:So increases was partially reversed. These findings demonstrated the interactions among FBs and sphingoid bases with G proteins and suggest a role of Ca2+- calmodulin in their interactions.