Trichothecene mycotoxins inhibit phosphoinositide hydrolysis in bovine platelets stimulated with platelet activating factor

Abstract

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.