AAL Toxin TA1

Fumonisins and Alternaria alternata lycopersici toxins: sphinganine analog mycotoxins induce apoptosis in monkey kidney cells.[Pubmed:8622958]

Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3461-5.

Fusarium moniliforme toxins (fumonisins) and Alternaria alternata lycopersici (AAL) toxins(AAL Toxin TA1,AAL Toxin TA2) are members of a new class of sphinganine analog mycotoxins that occur widely in the food chain. These mycotoxins represent a serious threat to human and animal health, inducing both cell death and neoplastic events in mammals. The mechanisms by which this family of chemical congeners induce changes in cell homeostasis were investigated in African green monkey kidney cells (CV-1) by assessing the appearance of apoptosis, cell cycle regulation, and putative components of signal transduction pathways involved in apoptosis. Structurally, these mycotoxins resemble the sphingoid bases, sphingosine and sphinganine, that are reported to play critical roles in cell communication and signal transduction. The addition of fumonisin B1 or AAL Toxin TA1,AAL Toxin TA2, to CV-1 cells induced the stereotypical hallmarks of apoptosis, including the formation of DNA ladders, compaction of nuclear DNA, and the subsequent appearance of apoptotic bodies. Neither mycotoxin induced cell death, DNA ladders, or apoptotic bodies in CV-1 cells expressing simian virus 40 large T antigen (COS-7) at toxin concentrations that readily killed CV-1 cells. Fumonisin B1 induced cell cycle arrest in the G1 phase in CV-1 cells but not in COS-7 cells.AAL Toxin TA1,AAL Toxin TA2 did not arrest cell cycle progression in either cell line. The induction of apoptosis combined with the widespread presence of these compounds in food crops and animal feed identifies a previously unrecognized health risk to humans and livestock. These molecules also represent a new class of natural toxicants that can be used as model compounds to further characterize the molecular and biochemical pathways leading to apoptosis.

Ultrastructural effects of AAL-toxin TA from the fungus Alternaria alternata on black nightshade (Solanum nigrum L.) leaf discs and correlation with biochemical measures of toxicity.[Pubmed:9839666]

Toxicon. 1998 Dec;36(12):1821-32

Ultrastructural effects of AAL Toxin TA1 from Alternaria alternata on black nightshade (Solanum, nigrum L.) leaf discs and correlation with biochemical measures of toxicity. In black nightshade (Solanum nigrum L.) leaf discs floating in solutions of AAL Toxin TA1 (0.01-200 microM) under continuous light at 25 degrees C, electrolyte leakage, chlorophyll loss, autolysis, and photobleaching were observed within 24 h. Electrolyte leakage, measured by the conductivity increase in the culture medium, began after 12 h with 200 microM AAL Toxin TA1, but was observed after 24 h with 0.01 to 50 microM AAL Toxin TA1, when it ranged from 25%) to 63% of total releasable electrolytes, respectively. After 48 h incubation, leakage ranged from 39% to 79% of total for 0.01 to 200 microM AAL Toxin TA1, respectively, while chlorophyll loss ranged from 5% to 32% of total, respectively. Ultrastructural examination of black night-shade leaf discs floating in 10 microM AAL Toxin TA1 under continuous light at 25 degrees C revealed cytological damage beginning at 30 h, consistent with the time electrolyte leakage and chlorophyll reduction were observed. After 30 h incubation chloroplast starch grains were enlarged in control leaf discs, but not in AAL Toxin TA1-treated discs, and the thylakoids of treated tissue contained structural abnormalities. After 36-48 h incubation with 10 microM AAL Toxin TA1, all tissues were destroyed with only cell walls, starch grains, and thylakoid fragments remaining. Toxicity was light-dependent, because leaf discs incubated with AAL Toxin TA1 in darkness for up to 72 h showed little phytotoxic damage. Within 6 h of exposure to > or =0.5 microM toxin, phytosphingosine and sphinganine in black nightshade leaf discs increased markedly, and continued to increase up to 24 h exposure. Thus, phy siological and ultrastructural changes occurred in parallel with disruption of sphingolipid synthesis, consistent with the hypothesis that AAL Toxin TA1 causes phytotoxicity by interrupting sphingolipid biosynthesis, thereby damaging cellular membranes.