Magnesium tanshinoate B protects endothelial cells against oxidized lipoprotein-induced apoptosis.
The activation of c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in the induction of cell apoptosis. We previously reported that magnesium tanshinoate B (MTB), a compound purified from a Chinese herb danshen (Salvia miltiorrhiza), could inhibit ischemia/reperfusion-induced myocyte apoptosis in the heart. The objective of the present study was to investigate whether MTB can prevent oxidized lipoprotein-induced apoptosis in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were incubated with copper-oxidized very low density lipoprotein (Cu-OxVLDL) or copper-oxidized low density lipoprotein (Cu-OxLDL). Treatment of cells with Cu-OxVLDL or Cu-OxLDL resulted in a 3-fold increase in the JNK activity. The amount of cytochrome c released and the activity of caspase-3 in cells treated with Cu-OxVLDL or Cu-OxLDL were significantly elevated, indicating the occurrence of apoptosis. The presence of MTB was able to abolish the JNK activation, cytochrome c release, and caspase-3 activation induced by Cu-OxVLDL or Cu-OxLDL, resulting in a marked reduction in apoptosis in endothelial cells. The data from this study indicate that oxidized lipoproteins induce apoptosis in endothelial cells. We postulate that the inhibition of the JNK signaling pathway by MTB is a key mechanism that protects these cells from oxidized lipoprotein-induced apoptosis.
Au-Yeung
Kathy K W
KK
Canadian Centre for Agri-Food Research in Health and Medicine, University of Manitoba, Winnipeg, MB R2H 2A6, Canada.
O
Karmin
K
Choy
Patrick C
PC
Zhu
Da-yuan
DY
Siow
Yaw L
YL
D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000633:toxicity*; D008274:Magnesium / Q000494:pharmacology*; D010618:Phenanthrolines / Q000494:pharmacology*
D000975:Antioxidants; D008077:Lipoproteins, LDL; D010618:Phenanthrolines; C099252:oxidized low density lipoprotein; C420242:magnesium tanshinoate B; D045304:Cytochromes c; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D008274:Magnesium