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Is fumonisin B1 responsible for equine leucoencephalomalacia?
530
Tenth World Congress
Isfumonisin B 1 responsible for equine leucoencephalomalacia? D. LAURENT,F. PELLEGRIN,F. KOHLER, R. COSTA, J. TtIEVENON, P. DEMERSEMAN, J. GUILLAUMEL and N. PLATZER (ORSTOM, BP A5, Noumta Cedex, Nouvelle-Caledonie). FUMON1SIN B~ injected intravenously into two horses induced leukoencephalomalacia preceded by hepatic symptoms; on the other hand, oral administration of this mycotoxin seemed to be innocuous. Fumonisin A l, N-acetylated derivative of fumonisin B t was administered orally to a mare. The absence of symptoms, both hepatic and nervous, seems to disprove the hypothesis of a nonassimilable zwitterion form that is fumonisin B~ in its natural form. This experiment confirms that fumonisins should not be regarded as the only molecules responsible for equine leucoencephalomalacia.
Effects of phospholipase A 2 neurotoxins on cAMP-activated phosphorylation of synaptic proteins. D.L. LEATI-WatMAN and J.L. MIDDLEBROOK (Department of Toxinology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, U.S.A.). PnOSPnOUPASEA 2 (PLAz) neurotoxins are potent inhibitors of the depolarization-induced release of acetylcholine from presynaptic nerve terminals. Recent investigations have shown that the phosphorylation/dephosphorylation of certain presynaptic phosphoproteins may be involved in the mediation or modulation of neurotransmitter release (DECAMILLI and GREENGARD 1986; UENO and ROSENBERG 1990). In the present investigation, rat brain synaptosomes were used to measure the effects of several phospholipase A 2 neurotoxins on the phosphorylation of synaptic proteins. Taipoxin and textilotoxin elicited a 30-50% inhibition of calcium/ calmodulin-regulated phosphorylation, while Naja naja atra PLA 2 produced only a marginal inhibition, results similar to UENO and ROSErCaERG(1990). In contrast, cyclic nucleotide-(cAMP) activated phosphorylation was potentiated 2-5-fold in synaptosomal lysates prepared from intact rat brain synaptosomes preincubated with taipoxin, textilotoxin or N. n. atra PLA 2. This effect was concentration dependent, and the non-neurotoxic (but highly enzymatic) N. n. atra PLA 2 was approximately 100-fold more potent than taipoxin or textilotoxin. The enhanced phosphorylation was observed in polypeptides with apparent mol. wts between 40,000 and 120,000 as determined by SDS-PAGE. Preincubation of synaptosomes with toxins in the presence of calcium was required to achieve maximal effect. Our results suggest that the potentiation of cAMP-activated phosphorylation by phospholipases A 2 may be related to their enzymatic activities, but correlates poorly with neurotoxicity. DECAM1LLI, P. and GREENGARD,P. (1986) Biochem. Pharmac. 35, 4349~1357. UENO, E. and ROSENn~G, P. (1990) Toxicon 28, 1423-1437.
Amphipathic regions in channel-forming bacterial toxins. F.J. LEBEDA,I D.C. HACK2 and M . K . GENTRY3 (INeurotox. Br., Pathophys, Div., U.S. Army Med, Res. Inst. Chem. Def., Aberdeen Prov. Grud., MD 21010-5425; 2Virology Division, U.S. Army Med. Res. Inst. Infect. Dis. Frederick, MD 21702-5011; 3Biochem. Chem. Br., Div. Biochem., Walter Reed Army Inst. Res., Wash. D.C. 20307-5100, U.SIA.). THEORETICAL analyses of the primary and secondary structures of three dichain bacterial toxins were conducted to predict possible channel-forming regions. Sequence alignment studies revealed that botulinum type A (BoTxA) and tetanus toxin (TeTx) are about 63% similar. In contrast, only a short segment in the B-(heavy) chain of diphtheria toxin (DiTx) is similar to a region in the heavy (H) chains of these two Clostridial toxins. This short region in DiTx was predicted to be one of several, potentially amphipathic sequences (possibly transmembrane and multimeric) on the B-chain in diphtheria toxin. The regions in BoTx-A and TeTx that are similar to this short segment were also predicted to be amphipathic. Further analyses of BoTx-A and TeTx sequences predicted that there may be two to three additional transmembrane, amphipathic regions flanking the first segment. These theoretical results are consistent with the hypothesis that two heavy chains, each having three to four amphipathic #,-helical regions, act in a co-operative manner to form ionic channels.
Species difference in circulatory and respiratory effects o f sarafotoxin-b and endothelin-1. C. Y. LEE, W. W. LIN, Y. M. CImN and S. Y. LEE (Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C.). SA~,FOTOXaN S6b (STx-b) isolated from Atractaspis engaddensis snake venom and endothelin-1 (ET-I) derived from vascular endothelium are 2 l-residue peptides and exhibit striking structural and functional similarities. The circulatory and respiratory effects as well as the causes of death induced by STx-b and ET-I were compared in anaesthetized rats, mice and guinea-pigs. In rats, both peptides caused a transient hypotension followed by a sustained pressor effect, whereas no or little initial hypotension was observed in mice and guinea-pigs, respectively. Guinea-pigs are more susceptible to STx-b and ET-I than are rats and mice. ECG changes indicate
Tenth World Congress
Isfumonisin B 1 responsible for equine leucoencephalomalacia? D. LAURENT,F. PELLEGRIN,F. KOHLER, R. COSTA, J. TtIEVENON, P. DEMERSEMAN, J. GUILLAUMEL and N. PLATZER (ORSTOM, BP A5, Noumta Cedex, Nouvelle-Caledonie). FUMON1SIN B~ injected intravenously into two horses induced leukoencephalomalacia preceded by hepatic symptoms; on the other hand, oral administration of this mycotoxin seemed to be innocuous. Fumonisin A l, N-acetylated derivative of fumonisin B t was administered orally to a mare. The absence of symptoms, both hepatic and nervous, seems to disprove the hypothesis of a nonassimilable zwitterion form that is fumonisin B~ in its natural form. This experiment confirms that fumonisins should not be regarded as the only molecules responsible for equine leucoencephalomalacia.
Effects of phospholipase A 2 neurotoxins on cAMP-activated phosphorylation of synaptic proteins. D.L. LEATI-WatMAN and J.L. MIDDLEBROOK (Department of Toxinology, United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, U.S.A.). PnOSPnOUPASEA 2 (PLAz) neurotoxins are potent inhibitors of the depolarization-induced release of acetylcholine from presynaptic nerve terminals. Recent investigations have shown that the phosphorylation/dephosphorylation of certain presynaptic phosphoproteins may be involved in the mediation or modulation of neurotransmitter release (DECAMILLI and GREENGARD 1986; UENO and ROSENBERG 1990). In the present investigation, rat brain synaptosomes were used to measure the effects of several phospholipase A 2 neurotoxins on the phosphorylation of synaptic proteins. Taipoxin and textilotoxin elicited a 30-50% inhibition of calcium/ calmodulin-regulated phosphorylation, while Naja naja atra PLA 2 produced only a marginal inhibition, results similar to UENO and ROSErCaERG(1990). In contrast, cyclic nucleotide-(cAMP) activated phosphorylation was potentiated 2-5-fold in synaptosomal lysates prepared from intact rat brain synaptosomes preincubated with taipoxin, textilotoxin or N. n. atra PLA 2. This effect was concentration dependent, and the non-neurotoxic (but highly enzymatic) N. n. atra PLA 2 was approximately 100-fold more potent than taipoxin or textilotoxin. The enhanced phosphorylation was observed in polypeptides with apparent mol. wts between 40,000 and 120,000 as determined by SDS-PAGE. Preincubation of synaptosomes with toxins in the presence of calcium was required to achieve maximal effect. Our results suggest that the potentiation of cAMP-activated phosphorylation by phospholipases A 2 may be related to their enzymatic activities, but correlates poorly with neurotoxicity. DECAM1LLI, P. and GREENGARD,P. (1986) Biochem. Pharmac. 35, 4349~1357. UENO, E. and ROSENn~G, P. (1990) Toxicon 28, 1423-1437.
Amphipathic regions in channel-forming bacterial toxins. F.J. LEBEDA,I D.C. HACK2 and M . K . GENTRY3 (INeurotox. Br., Pathophys, Div., U.S. Army Med, Res. Inst. Chem. Def., Aberdeen Prov. Grud., MD 21010-5425; 2Virology Division, U.S. Army Med. Res. Inst. Infect. Dis. Frederick, MD 21702-5011; 3Biochem. Chem. Br., Div. Biochem., Walter Reed Army Inst. Res., Wash. D.C. 20307-5100, U.SIA.). THEORETICAL analyses of the primary and secondary structures of three dichain bacterial toxins were conducted to predict possible channel-forming regions. Sequence alignment studies revealed that botulinum type A (BoTxA) and tetanus toxin (TeTx) are about 63% similar. In contrast, only a short segment in the B-(heavy) chain of diphtheria toxin (DiTx) is similar to a region in the heavy (H) chains of these two Clostridial toxins. This short region in DiTx was predicted to be one of several, potentially amphipathic sequences (possibly transmembrane and multimeric) on the B-chain in diphtheria toxin. The regions in BoTx-A and TeTx that are similar to this short segment were also predicted to be amphipathic. Further analyses of BoTx-A and TeTx sequences predicted that there may be two to three additional transmembrane, amphipathic regions flanking the first segment. These theoretical results are consistent with the hypothesis that two heavy chains, each having three to four amphipathic #,-helical regions, act in a co-operative manner to form ionic channels.
Species difference in circulatory and respiratory effects o f sarafotoxin-b and endothelin-1. C. Y. LEE, W. W. LIN, Y. M. CImN and S. Y. LEE (Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C.). SA~,FOTOXaN S6b (STx-b) isolated from Atractaspis engaddensis snake venom and endothelin-1 (ET-I) derived from vascular endothelium are 2 l-residue peptides and exhibit striking structural and functional similarities. The circulatory and respiratory effects as well as the causes of death induced by STx-b and ET-I were compared in anaesthetized rats, mice and guinea-pigs. In rats, both peptides caused a transient hypotension followed by a sustained pressor effect, whereas no or little initial hypotension was observed in mice and guinea-pigs, respectively. Guinea-pigs are more susceptible to STx-b and ET-I than are rats and mice. ECG changes indicate