Proteomic analysis reveals multiple patterns of response in cells exposed to a toxin mixture.

We have used proteomic analyses to probe the responses induced by a pair of marine biotoxins, okadaic acid (OA) and gambierol (GB), added alone or in combination to a cultured cell line and carried out a preliminary investigation into the possible interactions between toxins possessing two different molecular mechanisms of action at a cellular level. When MCF-7 cells were treated with OA, we found that cellular levels of 30 proteins were significantly affected, including several isoforms of nonphosphorylated and phosphorylated hsp 27, as well as enzymes involved in the maintenance of nucleoside triphosphate pools and the control of redox states of the cell. When we repeated our analysis using GB, nine proteins were significantly affected, including some isoforms of nonphosphorylated hsp 27, as well as semenogelin-1, myosin-7, and the ATP synthase subunit delta. The combined addition of OA and GB to MCF-7 cells, in turn, affected 14 proteins, including some isoforms of nonphosphorylated and phosphorylated hsp 27, as well as myosin-7, the ATP synthase subunit delta, and enzymes involved in the control of redox states of the cell. If components affected by either OA or GB, as well as by the combined treatment, were classified according to the detected changes, two sets of data were obtained, including the components whose levels were found affected by the combined treatment, regardless of the effect observed after addition of only one agent, and those that had been found affected in cells that had been challenged with only one toxin but not when cells had been subjected to the combined treatment. Multiple patterns of responses to the toxin mixture were recorded in the two sets, consisting of both independent and interacting actions, among which we detected synergistic, similar, and antagonistic effects.