Aripiprazole/Sertraline Hydrochloride

The nectrotrophic fungus Alternaria alternata f.sp. lycopersici infects tomato plants of the genotype asc/asc by utilizing a host‐selective toxin, AAL‐toxin, that kills the host cells by inducing programmed cell death. Asc‐1 is homologous to genes found in most eukaryotes from yeast to humans, suggesting a conserved function. A yeast strain with deletions in the homologous genes LAG1 and LAC1 was functionally complemented by Asc‐1, indicating that Asc‐1 functions in an analogous manner to the yeast homologues. Examination of the yeast sphingolipids, which are almost absent in the lag1Δlac1Δ mutant, showed that Asc‐1 was able to restore the synthesis of sphingolipids. We therefore examined the biosynthesis of sphingolipids in tomato by labeling leaf discs with l‐[3‐3H]serine. In the absence of AAL‐toxin, there was no detectable difference in sphingolipid labeling between leaf discs from Asc/Asc or asc/asc leaves. In the presence of pathologically significant concentrations of AAL‐toxin however, asc/asc leaf discs showed severely reduced labeling of sphingolipids and increased label in dihydrosphingosine (DHS) and 3‐ketodihydrosphingosine (3‐KDHS). Leaf discs from Asc/Asc leaves responded to AAL‐toxin treatment by incorporating label into different sphingolipid species. The effects of AAL‐toxin on asc/asc leaflets could be partially blocked by the simultaneous application of AAL‐toxin and myriocin. Leaf discs simultaneously treated with AAL‐toxin and myriocin showed no incorporation of label into sphingolipids or long‐chain bases as expected. These results indicate that the presence of Asc‐1 is able to relieve an AAL‐toxin‐induced block on sphingolipid synthesis that would otherwise lead to programmed cell death.