Role of heme oxygenase-1 in high glucose and advanced glycation end-products-induced oxidative stress in THP-1 cells

Abstract

Objective To investigate the effects of heme oxygenase-1(HO-1)on oxidative stress in THP-1 cells incubated with high glucose and advanced glycation end-products(AGE).Methods THP-1 cells were incubated with normal glucose(5 mmoL/L),hish glucose(15 mmol/L)+AGE(100 μg/ml),high glucose+AGE+zinc protoporphyrin(ZnPP,inhibitor of HO-1),and ZnPP(normal glucose),respectively.The levels of reactive oxygen species(ROS).maiondialdehyde(MDA),and tumor necrosis factor-α(TNF-α)were determined in the four groups while expressions of HO-1 mRNA and protein were detected by RT-PCR and Western blotting respectively.Results The levels of ROS,MDA,and TNF-αin high glucose+AGE and ZnPP groups were hisher than those in normal glucose group(all P<0.05).The levels of ROS and TNF-α in high glucose+AGE+ZnPP group were even higher compared with high glucose+AGE group(all P<0.05),along with decreased expressions of HO-1 mRNA and protein(0.39±0.02 vs 0.89±0.09,0.38±0.00 vs 0.81±0.02,both P<0.05).Conclusions The oxidative injury and inflammation in THP-1 cells induced by high glacose and AGE age exaggerated by HO-1 inhibitor.HO-1 may play an important role in diabetic oxidative stress. Key words: Heme oxygenase-1; Zinc protoporphyrin; Advanced glycation end-products; Oxidative stress; THP-1 cells