Altered expression of base excision repair genes in response to high glucose-induced oxidative stress in HepG2 hepatocytes.

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.

MATERIAL/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.