title: Altered expression of base excision repair genes in response to high glucose-induced oxidative stress in HepG2 hepatocytes.
abstract: BACKGROUND
  It is widely accepted that chronic hyperglycemia induces DNA oxidative damage in type 2 diabetes, but little is known about the effect of hyperglycemia on the DNA repair system which plays a critical role in the maintenance of genomic DNA stability in diabetes.
  
  
  METHODS
  To investigate the alteration of base excision repair (BER) genes under hyperglycemia, the relative expression of the mRNAs of the BER genes--ogg1, polbeta, lig3, xrcc1, and parp1--were quantified using real-time PCR in HepG2 hepatocytes incubated with 5.5 mM or 30 mM glucose.
  
  
  RESULTS
  High levels of glucose induced ROS accumulation and DNA damage, paralleling the dynamic alterations of BER mRNA expression. Compared to 5.5 mM glucose-treated cells, ogg1 and polbeta mRNA expression transiently increased at day 1 and decreased after day 4 in cells exposed to 30 mM glucose. Exposure to 30 mM glucose increased the activity of PARP1, which led to reduced cellular NAD content and insulin receptor phosphorylation.
  
  
  CONCLUSIONS
  Exposure to high concentrations of glucose initially led to the increased expression of BER mRNAs to counteract hyperglycemia-induced DNA damage; however, long-term exposure to high glucose concentrations reduced the expression of mRNA from BER genes, leading to accumulated DNA damage.
authors: The Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, China.
authors: Jing
authors: J
authors: Pang
authors: Chao
authors: C
authors: Xi
authors: Yang
authors: Y
authors: Dai
authors: Huan
authors: H
authors: Gong
authors: Tie-mei
authors: TM
authors: Zhang
mesh_terms: D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics*; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005947:Glucose / Q000494:pharmacology*; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009243:NAD; D011065:Poly(ADP-ribose) Polymerases; D011972:Receptor, Insulin; D005947:Glucose