title: [Effects of metformin on apoptosis induced by advanced glycation end-products and expressions of caspase-3, Bax and Bcl-2 in human dermal fibroblasts in vitro].
abstract: OBJECTIVE
  To investigate the effect of metformin in protecting against advanced glycation end products (AGEs)-induced apoptosis in human primary dermal fibroblasts.
  
  
  METHODS
  Fibroblasts were exposed to 100, 200, or 300 µg/mL AGEs, 300 µg/mL bovine serum albumin (BSA), or 300 µg/mL AGEs and 1 mmol/L metformin for 24, 48, or 72 h. The exposed cells were examined for cell apoptosis using a cell counting kit. The expressions of caspase-3, Bax and Bcl-2 protein in the fibroblasts treated for 72 h were detected with Western blotting.
  
  
  RESULTS
  AGEs exposures caused significant dose- and time-dependent apoptosis in the fibroblasts. A 72-h exposure to 300 µg/mL AGEs resulted in obviously increased apoptosis of the fibroblasts compared to the control group (0.72 ± 0.02 vs 1 ± 0.04, P<0.05), and metformin significantly decreased AGEs-induced apoptosis (0.98 ± 0.02 vs 0.72 ± 0.02, P<0.05). The expressions of caspase-3 and Bax protein were significantly increased (P<0.05) and Bcl-2 protein expression was decreased (P<0.05) with a lowered Bcl-2/Bax ratio in AGEs-treated fibroblasts (P<0.05), and such changes were significantly reversed by metformin treatment (P<0.05).
  
  
  CONCLUSIONS
  Metformin can antagonize AGEs-induced apoptosis in human dermal fibroblasts by regulating the expressions of caspase-3, Bax and Bcl-2.
authors.affiliation: Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. E-mail: pangry88@163.com.
authors.forename: Ruoyu
authors.initials: R
authors.lastname: Pang
authors.forename: Meiping
authors.initials: M
authors.lastname: Guan
authors.forename: Zongji
authors.initials: Z
authors.lastname: Zheng
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Xue
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D017127:Glycation End Products, Advanced / Q000009:adverse effects*; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494826:BAX protein, human; C000595707:BCL2 protein, human; D017127:Glycation End Products, Advanced; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D008687:Metformin; C505407:CASP3 protein, human; D053148:Caspase 3