ARS | Publication request: FUMONISIN (FB) INHIBITION OF CA2+-CALMODULIN (CAM) ACTIVATION OF PHOSPHODIESTERASE (PDE) AND GTPASE

Submitted to: International Toxicology Congress
Publication Type: Abstract Only
Publication Acceptance Date: July 6, 1995
Publication Date: N/A

Technical Abstract: Fumonisins (FBs), mycotoxins produced by Fusarium moniliforme, have been associated with equine leukoencephalomalacia, porcine pulmonary edema, and, possibly, human esophageal cancer. Structurally, the backbone of FBs resembles that of sphingosine (So) and sphinganine (Sa). FB has been shown to alter de novo sphingolipid biosynthesis by inhibition of sphinganine N- acyltransferase. In vitro effects of FBs, Sa and So on elements of the signal transduction system and in vivo effects of FB1 on developing chick embryos were studied. Calmodulin (CaM) stimulation of Ca2+-CaM-dependent phosphodiesterase (PDE) was significantly inhibited by hydrolyzed FB1, Sa and So at concentrations from 5 x 10-7 to 5 x 10-6 M, but unaffected by FB1, FB2, or sphingomyelin. FBs were shown to inhibit G protein binding in vitro. FB1, HFB1 and FB2 produced concentration dependent inhibition of GTPase activities with IC50 of 1.1 x 10-4, 3.5 x 10-4 and 1.2 x 10-4 M, respectively. Alterations in the Sa:So ratio also produced inhibitory effects on GTPase activities. In chick embryos, FB1 produced slight alterations in mAChR and G protein binding. Ultrastructural studies revealed increased swelling of mitochondria and accumulation of glycogen in the liver and kidney.