BACKGROUND: Activations of death receptors and mitochondrial damage are well-described common apoptotic pathways. Recently, a novel pathway via endoplasmic reticulum (ER) stress has been reported.METHODS: We assessed the role of tauroursodeoxycholic acid (TUDCA) in inhibition of ER stress and its protective effect on advanced glycation end products (AGEs)-induced apoptosis in murine podocytes. Podocytes were incubated with increasing doses of AGEs for variable time periods. Apoptosis was quantitatively determined by flow cytometry detecting propidium iodide expression and annexin V binding simultaneously. Level of glucose-regulated protein 78 (ER stress marker) expression was determined by Western blot. Intracellular calcium concentration ([Ca(2+)](i)) was recorded by a laser confocal microscope and the Ca(2+) indicator Fluo-3 labeling.RESULTS: AGEs induced podocyte apoptosis and increased the expression of glucose-regulated protein 78 in a dose- and time-dependent manner as compared with bovine serum albumin. These changes were accompanied by a rapid rise in [Ca(2+)](i) of podocytes. TUDCA was capable of abolishing AGEs-induced expression of glucose-regulated protein 78 and subsequently inhibited apoptosis in a dose-dependent manner.CONCLUSION: We propose that ER stress plays an important role in AGEs-induced apoptosis and that TUDCA prevents apoptosis by blocking an ER stress-mediated apoptotic pathway. This novel mechanism of TUDCA action suggests new intervention methods for AGEs-induced apoptosis of mouse podocytes in diabetic nephropathy.
Animals Apoptosis