PTPRO Promotes Oxidized Low-Density Lipoprotein Induced Oxidative Stress and Cell Apoptosis through Toll-Like Receptor 4/Nuclear Factor κB Pathway.

Background/aims: Critical roles of phosphatase receptor type O (PTPRO) and toll-like receptor 4 (TLR4) have been implicated in inflammation. However, little is known about their functional effects on atherosclerosis (AS). We aim to study their potential function in AS.

Methods: An oxidized low-density lipoprotein (ox-LDL) induced AS model constructed with PTPRO over-expressing RAW264.7 cells and PTPRO knockout macrophages. Cell apoptosis was assayed by flow cytometry and fatty accumulation was evaluated by oil red staining. The production of ROS (reactive oxygen species), SOD (superoxide dismutase), MDA (malondialdehyde), TC (Triglyceride), and TG (total cholesterol) was evaluated. Western blot was performed to detect the expression of CD36, TLR4 and nuclear factor kB (NF-κB).

Results: PTPRO expression was promoted in a dose-dependent and time-dependent manner following ox-LDL challenging. In PTPRO-over-expressing cells, CD36 expression and the level of oil-red staining, TC and TG were increased; ROS production, MDA and level of cell apoptosis were improved, but SOD was reduced. However, in PTPRO knockout cells opposite results were found. TLR4 and NF-κB/p65 phosphorylation was significantly enhanced in PTPRO over-expressing cells, while significantly down-regulated in PTPRO knockout cells.

Conclusion: PTPRO plays ital roles in AS via promoting ox-LDL induced oxidative stress and cell apoptosis through TLR4/NF-κB pathway.