Oxysterols induced apoptosis in cultured smooth muscle cells through CPP32 protease activation and bcl-2 protein downregulation.
Previously we have shown that oxidized low density lipoprotein (Ox-LDL) induced apoptosis in vascular smooth muscle cells (VSMCs) and that this apoptosis contributed to oxysterol, 7-ketocholesterol. The aim in this present study was to identify the mechanism by which oxysterols induced apoptosis in VSMCs. We show that both 7-ketocholesterol and 25-hydroxycholesterol induced apoptosis, followed by a rapid decrease in bcl-2 protein in the cells. CPP32/Yamma inhibitor prevented apoptosis induced by 7-ketocholesterol and 25-hydroxycholesterol in VSMCs, whereas the exogenous cholesterol, which itself did not have any apoptotic activity, inhibited 25-hydroxycholesterol induced apoptosis but the 7-ketocholesterol-induced apoptosis was not affected. These results suggest that 25-hydroxycholesterol induced-apoptosis occurs by a different mechanism than 7-ketocholesterol induced-apoptosis.
Nishio
E
E
Department of Pharmacology, National Defense Medical College, Saitama, Japan.
Watanabe
Y
Y
D000818:Animals; D001013:Aorta, Thoracic; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D004789:Enzyme Activation / Q000187:drug effects; D004792:Enzyme Precursors / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007653:Ketocholesterols / Q000494:pharmacology*; D007700:Kinetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D011817:Rabbits
D015853:Cysteine Proteinase Inhibitors; D004792:Enzyme Precursors; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D019253:Proto-Oncogene Proteins c-bcl-2; C007997:25-hydroxycholesterol; D004247:DNA; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; C003001:7-ketocholesterol