Comparative proteomics analysis of midgut samples from Takifugu rubripes exposed to excessive fluoride: initial molecular response to fluorosis.

Comparative proteomic analysis was performed to identify proteins in the midgut of Takifugu rubripes (Fugu) in response to excessive fluoride. Sixteen fish were randomly divided into a control group and an experimental group. The control group was raised in soft water alone (F⁻= 0.4 mg/L), whereas the experimental group was raised in the soft water with sodium fluoride at a high concentration of 35 mg/L. After 3 days, proteins were extracted from the fish midgut and then subjected to two-dimensional (2-D) PAGE analysis. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF/TOF MS) was applied to identify the differential expressed proteins between the two groups. Among 377 and 528 proteins detected in the control and the treated groups, respectively, 17 proteins were up-regulated and 218 were down-regulated (P < 0.01) in the fluoride-treated group, compared with the control group. We further analyzed 17 up-regulated proteins by MALDI TOF/TOF MS and identified 12 of them by MASCOT, of which eight were known proteins. Consistent with their annotated functions, these proteins seem to be involved in apoptosis and other functions related to fluorosis. Our results provide initial insights into the effects of excessive fluoride exposure on physiological and biochemical functions of Fugu midgut as well as on the toxicological mechanism of fluoride in both fish and human.