Quantitative proteomic analysis of okadaic acid treated mouse small intestines reveals differentially expressed proteins involved in diarrhetic shellfish poisoning

Okadaic acid (OA) is a principal diarrhetic shellfish poisoning toxin produced by marine dinoflagellates. This study compared protein profiles of mice small intestines at four time points (0, 3, 6 and 24 h) after a single oral administration of 750 μg/kg OA, and identified the differentially expressed proteins using 2-D DIGE and MALDI-TOF-TOF mass spectrometry. The results showed that the toxin content of the intestines reached its peak 3 h after oral administration and then decreased rapidly. OA remarkably inhibited the intestinal PP activity but it recovered to the normal levels within 6 to 24 h. Electron microscope revealed the collapse of the villous architecture and the intestinal microvilli fell off at 3 h, but were repaired within 24 h. Notable damage to the intestinal ultrastructure was observed after oral administration. Comparison of the small intestine protein profiles at four time points revealed that 58 proteins were remarkably altered in abundance, and these proteins were involved in macromolecular metabolism, cytoskeleton reorganization, signal transduction, molecular chaperoning and oxidative stress, suggesting that OA toxicity in mouse intestines was complex and diverse, and that multiple proteins other than PP were involved in the diarrhetic process. Villin 1 and hnRNP F might be the key triggers inducing diarrhea in the mouse small intestines.

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► Okadaic acid is the principal diarrhetic shellfish poisoning toxin produced by marine dinoflagellates.
► The precise mechanism of OA resulting in diarrhea and its subsequent effects in mammals are not well established.
► Using the 2-D DIGE and MALDI-MS-MS, we identified 58 proteins that associate with diarrhea including Villin and hnRNP F.
► OA toxicity in mice is complex and diverse and multiple proteins are involved in the diarrhetic process.