Identification of Temporal Differentially Expressed Protein Responses to Microcystin in Human Amniotic Epithelial Cells

• Published in: Chemical research in toxicology Vol. 22; no. 1; pp. 41 - 51
• Main Authors: Fu, Wenyu, Yu, Yingnian, Xu, Lihong
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.01.2009
• Subjects: Amnion - cytology; Cell Line; Electrophoresis, Gel, Two-Dimensional; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Humans; Microcystins - pharmacology; Microcystins - toxicity; Peptide Mapping; Protein Array Analysis; Proteins - classification; Proteins - metabolism; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Time Factors; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx800396p

The increased distribution of microcystins (MCs) has become a global issue. However, the MC response machinery has not been completely studied and elucidated until now. Our previous dose-related analysis has revealed that different concentrations of mirocystin-RR (MC-RR) can trigger comprehensive and various alterations in the protein expression profile using a proteomic approach. To further dissect the kinetics of cellular responses associated with MC-RR cytotoxic effects, the present study has set out to investigate the temporal protein expression pattern at three time points (3, 12, and 24 h after exposure). The relative intensity has changed significantly in MC-RR-treated FL cells, as compared with the control, in a total of 127 protein spots. One hundred and two proteins have been further identified with high confidence by peptide mass fingerprinting. These proteins can be categorized into diverse functional classes such as signal transduction, apoptosis, protein degradation, cell cycle, cell differentiation, transporter, and so forth. The wide range of different proteins involved suggests that MC-RR has profound effects on the biological response and toxic consequences of the affected cells. The identification of p53 and its potential targets confirms a known role for p53 in the MC-RR response. Moreover, it is noteworthy that MC-RR can up-regulate the expression of the PP2A A subunit and down-regulate the expression of a number of proteins implicated in the ubiquitin-proteasome pathway. Therefore, the present expression data provide a global view of dynamic changes in cell responses to MC-RR and, more importantly, generate novel hypotheses regarding MC-RR-responsive mechanisms.