Tanshinone IIA protects against methylglyoxal-induced injury in human brain microvascular endothelial cells.
Tanshinone IIA is one of the major diterpenes from Salvia miltiorrhiza Bunge and has been shown to possess a protective effect on the endothelial cells. The present study aimed to investigate whether tanshinone IIA could protect against methylglyoxal (MGO)-induced injury in human brain microvascular endothelial cells (HBMEC). Using cultured HBMEC, cell viability was measured by MTT assay and trypan blue dye exclusion test. Cellular oxidative stress was measured by production of reactive oxygen species (ROS), thiobarbituric acid reactive substances (TBARS) and H2O2. AnnexinV/PI staining and western blot were performed to determine cell apoptosis and protein expression. We found that MGO treatment caused a concentration and time-dependent decrease in cell viability, which was inhibited by pretreatment with tanshinone IIA. Exposure to MGO promoted the accumulation of AGEs, and production of ROS, TBARS and H2O2 in the cultured HBMEC, which were inhibited by tanshinone IIA pretreatment. Addition of tanshinone IIA significantly reduced MGO-induced cell apoptosis as shown by flow cytometry. On the molecular level, tanshinone IIA administration altered the expression of apoptosis-related proteins such as p53, Bax, Bcl-2 and cyto C. In addition, MGO treatment remarkably increased the phosphorylation of MAPK family including p38, JNK and ERK. By contrast, addition of tanshinone IIA inhibited the activation of MAPK family members. These data indicated that tanshinone IIA could protect against MGO-induced cell injury through inhibiting MAPK activation in HBMEC.
Department of Cadre Ward, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003, China.
Wen-Jing
WJ
Zhou
Department of Cadre Ward, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003, China.
Qi-Feng
QF
Gui
Department of Cadre Ward, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003, China.
Yue
Y
Wu
Department of Cadre Ward, The First Affiliated Hospital, Zhejiang University School of Medicine Hangzhou 310003, China.
Yun-Mei
YM
Yang
MAPK; Tanshinone IIA; apoptosis; human brain microvascular endothelial cells; methylglyoxal