title: Effect of taurine-conjugated ursodeoxycholic acid on endoplasmic reticulum stress and apoptosis induced by advanced glycation end products in cultured mouse podocytes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Cui Ping
authors.initials: CP
authors.lastname: Liu
authors.forename: Kuan Feng
authors.initials: KF
authors.lastname: Xu
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Mao
authors.forename: Yi Bing
authors.initials: YB
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Jun Wei
authors.initials: JW
authors.lastname: Yang
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D005786:Gene Expression Regulation; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism; D051379:Mice; D018613:Microscopy, Confocal; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism*; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D013997:Time Factors; D014580:Ursodeoxycholic Acid / Q000737:chemistry*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D017127:Glycation End Products, Advanced; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D013654:Taurine; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid; D002118:Calcium