High Concentrations Of Glucose-induced Apoptosis In HepG2Cells And Associated With Endoplasmic Reticulumstress And Their Regulation Mechanism

Objective To investigate high concentration of glucose-induced proliferation、migration and apoptosis in HepG2cells and to explore its association with theendoplasmic reticulum stress, as well as its possible regulation mechanism. MethodsHepG2cells were treated with different concentrations of glucose, and were dividedinto normal group (glucose concentration of5.5mmol/L)、high concentrations ofglucose (glucose concentration of25,40,100,150,200mmol/L) and mannitol group(glucose concentration of5.5mmol/L+19.5,34.5,94.5,144.5,194.5mmol/Lmannitol). The growth and proliferation of HepG2cells were analyzed by microscopyand MTT respectively. The apoptosis of HepG2cells, which were treated with highconcentrations of glucose, was detected by Hoechst staining and flow cytometry. Theexpression of apoptosis-related protein Bcl-2, Bak, Bax, p53, Grim19, Survinin andNF-κB were studied by Western blot, and the activity of Caspase3was analyzed byCaspase3kit. The scarification test was used to study the effect of high concentrationof glucose on HepG2cells growth and migration. Western blot was used to detect theexpression of PP38/p38, P-JNK/JNK, BIP and CHOP in HepG2cells treated with highconcentration of glucose. Results High concentration of glucose could inhibit thegrowth of HepG2cells; Moreover, high concentration of glucose could also induceapoptosis in a concentration dependent manner; Western blot showed that highconcentration of glucose down-regulated Bcl-2and Survinin, and increased Bak, Bax,p53, Grim19and NF-κB expression and inhibited migration of HepG2cells and may activate JNK/p38MAPK signal transduction pathway by increasing thephosphorylation levels of JNK and p38, down-regulating BIP and increasing CHOPexpression （P＜0.05）. Conclusions High concentration of glucose can induceapoptosis in HepG2cells by inhibiting the growth, proliferation and migration. Itsmechanism may be that high concentration of glucose can initiate the endoplasmicreticulum stress, regulate-apoptosis genes and certain tumor suppressor genes, andtheir coordination with MAPK signalling pathway at the same time.