Oxidized low-density lipoprotein sensitizes human vascular smooth muscle cells to FAS (CD95)-mediated apoptosis.
1. It was investigated in the present study whether oxidized low-density lipoprotein (oxLDL) was implicated in the susceptibility of human vascular smooth muscle cells (VSMC) to Fas-mediated death. Human fetal aorta smooth muscle cells were treated with agonistic anti-Fas antibody (CH11) and oxLDL and cell death was then determined by viability and DNA fragmentation. 2. The results of the present study show that cross-linking of Fas receptor with anti-Fas antibody in the presence of oxLDL induced death and DNA fragmentation in human VSMC, which were blocked by the caspase inhibitor z-VAD.fmk, followed by the upregulation of cell surface Fas. 3. The data indicate that oxLDL is implicated in death in VSMC and provide evidence that oxLDL is involved in Fas signal transduction. The present study proposes a novel mechanism(s) by which VSMC become susceptible to Fas ligand. 4. One of the mechanisms proposed by which oxLDL upregulates cell surface Fas is by inhibiting the degradation of Fas through the ubiquitin-proteasome pathway.
Takarada
Shigeho
S
Department of Cardiovascular Medicine, Wakayama Medical University, Japan.
Imanishi
Toshio
T
Hano
Takuzo
T
Nishio
Ichiro
I
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000166:cytology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D004622:Embryo, Mammalian; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology* / Q000502:physiology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D015854:Up-Regulation; D019014:fas Receptor / Q000096:biosynthesis* / Q000187:drug effects / Q000276:immunology
D000590:Amino Acid Chloromethyl Ketones; D000906:Antibodies; D061945:Caspase Inhibitors; D007976:Leupeptins; D008077:Lipoproteins, LDL; D009097:Multienzyme Complexes; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor; C099252:oxidized low density lipoprotein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde