Temporary membrane distortion of vascular smooth muscle cells is responsible for their apoptosis induced by platelet-activating factor-like oxidized phospholipids and their degradation product, lysophosphatidylcholine.
To obtain information about the mechanism of apoptosis induced by oxidized low density lipoproteins (oxLDL) in atherosclerotic plaques, we examined the effects of lysophosphatidylcholine (LPC) and platelet-activating factor (PAF)-like lipids (PAF-LL), which can be derived from oxLDL, on rat vascular smooth muscle cells (VSMC). All the lipids with different structures examined induced apoptosis of VSMC, so we studied the mechanism of induction of apoptosis by LPC. LPC-induced apoptosis was inhibited by alpha-tocopherol (alpha-T) and cholesterol (Chol), but not by other antioxidants such as palmitoyl ascorbic acid and PAF receptor antagonist. The cells temporarily became spherical and highly permeable before induction of apoptosis, and their change in shape was prevented by alpha-T and Chol. From these results, we suggest that the apoptosis induced by oxLDL-derived phospholipids in VSMC is caused by temporary membrane distortion, not through specific receptors.
Kogure
Kentaro
K
Faculty of Pharmaceutical Sciences, University of Tokushima, Shomachi-1, Tokushima 770-8505, Japan.
Nakashima
Sawa
S
Tsuchie
Akiko
A
Tokumura
Akira
A
Fukuzawa
Kenji
K
D000818:Animals; D001011:Aorta; D017209:Apoptosis; D002462:Cell Membrane / Q000648:ultrastructure*; D002463:Cell Membrane Permeability; D048429:Cell Size / Q000187:drug effects; D002784:Cholesterol / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D024502:alpha-Tocopherol / Q000494:pharmacology
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D010972:Platelet Activating Factor; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D024502:alpha-Tocopherol