Phorbol 12-myristate 13-acetate induced changes in chicken enterocytes

Authors: Rath, Narayan; GUPTA, ANAMIKA - University Of Arkansas; LIYANAGE, ROHANA - University Of Arkansas; LAY, JACKSON - University Of Arkansas

Submitted to: Proteomics Insights
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/26/2019
Publication Date: 4/12/2019
Citation: Rath, N.C., Gupta, A., Liyanage, R., Lay, J. 2019. Phorbol 12-myristate 13-acetate induced changes in chicken enterocytes. Proteomics Insights. 10:1-13. https://doi.org/10.1177/1178641819840369.
DOI: https://doi.org/10.1177/1178641819840369

Interpretive Summary: Many intestinal diseases are associated to the breach of barrier function of cells lining the intestine which results in the entrance of disease causing bacteria or toxins into the system. We used a chemical that produces cellular changes which resembles this phenomenon using intestinal cell culture then studied whether there are changes in proteins of these cells that underlie this phenomenon. Our results suggest that this chemical affects mitochondrial metabolism causing cellular shrinkage leading to the increase in the permeability of intestinal lining cells.

Technical Abstract: Increased intestinal epithelial permeability has been linked to many enteric diseases because it allows easy access of microbial pathogens and toxins into the system. In poultry production, the restrictions in the use of antibiotic growth promoters, has increased the chances of birds being susceptible to different enteric diseases. Thus, understanding the mechanisms which compromise intestinal function is pertinent. Based on our previous observation which showed the primary chicken enterocytes in culture, undergoing dystrophic changes on treatment with phorbol myristate acetate (PMA), we surmised that this model which appeared to mimic increased intestinal permeability, could help to understand the mechanisms of this problem. Since genomic and proteomic changes are associated with many physiological and pathological problems, we were interested to find whether some proteomic changes underlie the morphological alterations in the enterocytes induced by PMA. We exposed primary enterocyte cultures to a sub lethal concentration of PMA and extracted the proteins and analyzed by mass spectrometry for differentially regulated proteins. Our results showed that PMA affected several biological processes, negatively impacted their energy metabolism, nuclear activities, and differentially regulated the levels of several stress proteins, chaperon, cytoskeletal, and signal transduction proteins which seem relevant in the cause of enterocyte dystrophy. PMA affected signal transduction activities also raises the possibilities of their increased susceptibility to pathogens. The changes in enterocyte integrity can make intestine vulnerable to invasion by microbial pathogens and disrupt gut homeostasis.