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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
Authors:Kogure Kentaro  Nakashima Sawa  Tsuchie Akiko  Tokumura Akira  Fukuzawa Kenji
Institution:Faculty of Pharmaceutical Sciences, University of Tokushima, Shomachi-1, Tokushima 770-8505, Japan.
Abstract: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.
Keywords:VSMC  vascular smooth muscle cells  LDL  low-density lipoprotein  oxLDL  oxidatively modified LDL  LPC  lysophosphatidylcholine  GPC  glycerophosphocholine  PAF  platelet-activating factor  PAF-LL  PAF-like oxidized phospholipids  DMEM  Dulbecco’s modified Eagle’s medium  PBS  phosphate-buffered saline  LDH  lactate dehydrogenase  acyl-C16/C4  1-stearoyl-2-succinyl-GPC  acyl-C18/C4  1-palmitoyl-2-succinyl-GPC  acyl-C16/C5  1-palmitoyl-2-glutaryl-GPC  alkyl-C16/C4  1-O-hexadecyl-2-succinyl-GPC  alkyl-C16/C5  1-O-hexadecyl-2-glutaryl-GPC  α-T  α-tocopherol  Chol  cholesterol
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