AAL Toxin TB1

Comparison of the cytotoxicities of Fusarium metabolites and Alternaria metabolite AAL-toxin to cultured mammalian cell lines.[Pubmed:8507101]

Arch Environ Contam Toxicol. 1993 May;24(4):473-7.

Four water-soluble Fusarium metabolites (fumonisin B1, fusaric acid, butenolide and moniliformin), water-insoluble pigment (8-O-methylbostrycoidin), and an Alternaria metabolite AAL Toxin TB1) were tested for relative cytotoxicity to five established mammalian cell lines. Butenolide was the most cytotoxic to all five cell lines. LC50s were; 1 microgram/ml to rat hepatoma (RH) (tumors derived from parenchymal cells), 7 micrograms/ml to baby hamster kidney (BHK-21) fibroblast cells, and 15 micrograms/ml to McCoy mouse (MM) fibroblast cells: LC100s were 1 microgram/ml to Chinese hamster ovary (CHO) fibroblast cells, and 5 micrograms/ml to dog kidney (MDCK) fibroblast cells. Fusaric acid was cytotoxic to the MDCK, MM, RH, and CHO cell lines; moniliformin was cytotoxic to the RH, CHO, and MDCK, cell lines. The pigment, however, was cytotoxic only to RH and CHO cell lines. Fumonisin B1 and a related toxin, AAL Toxin TB1, at a high dose level (100 micrograms/ml) were not cytotoxic to the RH, BHK, MM, CHO and MDCK cell lines. AAL Toxin TB1 was used as a positive control, and inhibited all cell lines at the nanogram level. The difference in response of these five cell lines to the toxic metabolites, that were noted in this study, was then used to evaluate nine HPLC fractions obtained from a methanol-water extract of an F. moniliforme culture. The results indicated that this type of cytotoxicity assay may be useful in following the isolation of metabolites from extracts of Fusarium culture, especially F. moniliforme.

An extensive microarray analysis of AAL-toxin-induced cell death in Arabidopsis thaliana brings new insights into the complexity of programmed cell death in plants.[Pubmed:15141304]

Cell Mol Life Sci. 2004 May;61(10):1185-97.

A T-DNA knockout of the Arabidopsis homologue of the tomato disease resistance gene Asc was obtained. The asc gene renders plants sensitive to programmed cell death (PCD) triggered by the fungal AAL Toxin TB1. To obtain more insights into the nature of AAL-toxin-induced cell death and to identify genes of potential importance for PCD, we carried out transcription profiling of AAL-toxin-induced cell death in this knockout with an oligonucleotide array representing 21,500 Arabidopsis genes. Genes responsive to reactive oxygen species (ROS) and ethylene were among the earliest to be upregulated, suggesting that an oxidative burst and production of ethylene played a role in the activation of the cell death. This notion was corroborated by induction of several genes encoding ROS-generating proteins, including a respiratory burst oxidase and germin oxalate oxidase. Cytochemical studies confirmed the oxidative burst and, in addition, showed synthesis of callose, a feature of the hypersensitive response. A diverse group of transcription factors was also induced. These events were followed by repression of most of the auxin-regulated genes known to be involved in growth and developmental responses. All photosynthesis-related genes were repressed. Blocking the synthesis of ethylene or NO significantly compromised cell death. In addition, we identified a heterogeneous group of early-induced genes, some of them never before associated with PCD. The group of early-induced genes included a number of proteases that were previously implicated in developmentally regulated types of PCD, suggesting a more principal role for these proteases in the PCD process. These findings provide new insights into the molecular mechanisms of plant PCD.