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Effect of taurine-conjugated ursodeoxycholic acid on endoplasmic reticulum stress and apoptosis induced by advanced glycation end products in cultured mouse podocytes.
Chen, Yu; Liu, Cui Ping; Xu, Kuan Feng; Mao, Xiao Dong; Lu, Yi Bing; Fang, Li; Yang, Jun Wei; Liu, Chao.
Afiliação
  • Chen Y; Department of Endocrinology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, PR China.
Am J Nephrol ; 28(6): 1014-22, 2008.
Article em En | MEDLINE | ID: mdl-18648192
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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Taurina / Ácido Tauroquenodesoxicólico / Ácido Ursodesoxicólico / Produtos Finais de Glicação Avançada / Apoptose / Retículo Endoplasmático / Podócitos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Nephrol Ano de publicação: 2008 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Taurina / Ácido Tauroquenodesoxicólico / Ácido Ursodesoxicólico / Produtos Finais de Glicação Avançada / Apoptose / Retículo Endoplasmático / Podócitos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Nephrol Ano de publicação: 2008 Tipo de documento: Article