In earlier studies, we have found UDCA protects against DCA-induced DNA damage and activation of the NF-
κ
B pathway in biopsies from patients with Barrett’s esophagus and also in two benign Barrett’s cell lines (BAR-T and BAR10-T cells).
UDCA blocks DCA-induced ROS generation and increases expression of the anti-oxidant GPX1. In the recent 3 months, we identified additional anti-oxidant enzymes affected by UDCA treatment. To demonstrate that these anti-oxidant enzymes were relevant to the protective effects of UDCA, we inhibited these enzymes using siRNA and studied the effects on DCA-induced DNA damage.
Results: We found UDCA also caused a significant increase expression of catalase
(CAT) in BAR-T and BAR10-T cell lines, but not SOD1 or SOD2 by Western blotting.
We transfected Barrett’s cells lines with siRNA for GPX1 and CAT. We found that 48 hours after transfection is the time point at which we observed maximal knockdown of gene expression.
Conclusion: UDCA increases expression of the anti-oxidant GPX1 and CAT, which maybe an important mechanism of UDCA protection.
Some of these data were submitted as an abstract to the international meeting of the
American Gastroenterological Association and have been accepted as an oral presentation in the meeting. In this month, I also prepared, reviewed, and finished the slides for the oral presentation.
I have reviewed this report with Dr. Peng.