Trichothecene mycotoxins inhibit phosphoinositide hydrolysis in bovine platelets stimulated with platelet activating factor.
The effects of the trichothecene mycotoxins, acetyl T-2 toxin, T-2 toxin, HT-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON) and T-2 tetraol on phospholipid turnover were determined in bovine platelets prelabelled with [1-14C]arachidonic acid (AA). In resting, non-stimulated platelets exposed to acetyl T-2 toxin, a marked decrease in [1-14C]phosphatidylinositol (PI) along with a marked increase in [1-14C]phosphatidic acid (PA) were observed, whereas T-2 toxin, and HT-2 toxin only induced a significant increase in [1-14C]PA. In contrast, in platelet activating factor (PAF)-stimulated platelets, the mycotoxins were found to suppress both the agonist-induced loss of [1-14C]PI and the appearance of [1-14C]PA with acetyl T-2 toxin being the most effective and T-2 toxin, HT-2 toxin, and DAS essentially equally effective. T-2 tetraol and DON did not affect phospholipid metabolism either in unstimulated or PAF stimulated platelets. The alterations in [1-14C]PI and [1-14C]PA suggest that the inhibitory toxins may activate a specific phospholipase C (PLC) in the unstimulated platelets and then impede further PLC activation in PAF-stimulated platelets.
Grandoni
K M
KM
Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Ontario, Canada.
Gentry
P A
PA
Holub
B J
BJ
Yagen
B
B
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002250:Carbon Radioisotopes; D002417:Cattle; D003864:Depression, Chemical; D006868:Hydrolysis; D066298:In Vitro Techniques; D010716:Phosphatidylinositols / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D014255:Trichothecenes / Q000633:toxicity*
D002250:Carbon Radioisotopes; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D014255:Trichothecenes