title: Glucagon-like peptide-1 inhibits the receptor for advanced glycation endproducts to prevent podocyte apoptosis induced by advanced oxidative protein products.
abstract: OBJECTIVE
  To investigate whether and how glucagon-like peptide-1 (GLP-1) can protect podocytes from apoptosis induced by advanced oxidative protein products (AOPPs).
  
  
  METHODS
  Murine podocytes were stimulated with 200 μg/ml AOPP for 48 h in the presence or absence of GLP-1. Cell viability was assessed using the cell counting kit-8 assay. Podocyte apoptosis was detected by flow cytometry and Hoechst 33258 staining. Superoxide radical production was assayed using lucigenin-enhanced chemiluminescence, and Western blotting was used to measure expression of RAGE, NADPH oxidase subunits p47phoxand gp91phox, as well as apoptosis-associated proteins p53, Bax, Bcl-2 and caspase-3.
  
  
  RESULTS
  Incubating podocytes with AOPPs reduced cell viability, triggered changes in cell morphology and promoted apoptosis. GLP-1 partially inhibited AOPP-induced apoptosis, O2-overproduction, and AOPP-induced expression of RAGE. GLP-1 inhibited expression of p47phoxand gp91phoxin AOPP-treated podocytes, and it attenuated AOPP-induced expression of p53, Bax and cleaved caspase-3, whereas it restored expression of Bcl-2.
  
  
  CONCLUSIONS
  GLP-1 partially inhibits AOPP-induced apoptosis in podocytes, perhaps by interfering with the AOPP-RAGE axis, decreasing oxidative stress and inhibiting the downstream p53/Bax/caspase-3 apoptotic pathway. GLP-1 may be a useful anti-apoptotic agent for early intervention in diabetic nephropathy.
authors.affiliation: Department of Pathophysiology, Key Laboratory for Shock and Microcirculation Research of Guangdong Province, Southern Medical University, Guangzhou, China; Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shuang-Shuang
authors.initials: SS
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Yue Bei People's Hospital, Shaoguan, China.
authors.forename: Zhou-Yi
authors.initials: ZY
authors.lastname: Xiong
authors.affiliation: Department of Endocrinology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address: rubychen1966@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pathophysiology, Key Laboratory for Shock and Microcirculation Research of Guangdong Province, Southern Medical University, Guangzhou, China. Electronic address: bing@smu.edu.cn.
authors.forename: Qiao-Bing
authors.initials: QB
authors.lastname: Huang
mesh_terms: D062107:Advanced Oxidation Protein Products / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D051379:Mice; D009249:NADP / Q000737:chemistry; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry; D050199:Podocytes / Q000166:cytology / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D013481:Superoxides / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D062107:Advanced Oxidation Protein Products; D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D016159:Tumor Suppressor Protein p53; D013481:Superoxides; D009249:NADP; D052216:Glucagon-Like Peptide 1; D010100:Oxygen
keywords: Advanced oxidative protein products; Apoptosis; Glucagon-like peptide-1; Podocytes; Receptor for advanced glycation endproducts