PGC-1andalpha; and p38 MAPK are involved in uncoupling protein 2-dependent reactive oxygen species production in renal tubular epithelial cells

Object: The objective was to investigate Uncoupling protein 2 (UCP2)-dependent Reactive oxygen species (ROS) production in renal tubular epithelial cells treated with high glucose. Methods: In this study, we investigated the associations among PGC-1α, p38 MAPK and UCP2 in HK-2 cells treated with high glucose. Target genes overexpression and silence were obtained by plasmid transfection, and SB203580 was applied as a p38 MAPK inhibitor. The mutual effect of these three proteins was evaluated by RTPCR and western blot. ROS production was detected by a fluorescent probe. Results: We found that UCP2 overexpression enhanced PGC-1α expression, as well as inhibited p38 MAPK activation and ROS generation. These changes were reversed by UCP2 siRNA. However, neither PGC-1α nor p38 MAPK could exert significant influence on the expressions of the other two proteins, although their capacity to regulate ROS was demonstrated. Conclusion: These results indicate UCP2 plays a pivotal and relatively upstream role in oxidative stress induced by high glucose in renal tubular epithelial cells.