K. Kogure et al. / Chemistry and Physics of Lipids 126 (2003) 29–38
37
Domanico, 1992), the binding of LPC molecules
to the plasma membrane of VSMC would be very
fast. Lowering the membrane microviscosity by LPC
Besterman, J.M., Domanico, P.L., 1992. Association and
metabolism of exogenously-derived lysophosphatidylcholine
by cultured mammalian cells: kinetics and mechanisms.
Biochemistry 31, 2046–2056.
Bligh, E.G., Dyer, W.J., 1959. A rapid method of total lipid
extraction and purification. Can. J. Biochem. Physiol. 37, 911–
917.
(Ghosh et al., 2002) was also suggested to be a reason
for its effect. The temporary loss of membrane barrier
function and cell shape change would be due to mod-
ification by LPC of the physicochemical properties of
the plasma membrane, possibly by distortion of ar-
rangement of membrane lipid, and result in induction
of apoptosis. Perhaps, LPC molecule temporarily lo-
calized in the outer leaflet of the lipid bilayer caused
membrane distortion as observed in the erythrocyte
membrane (Bergmann et al., 1981; Tamura et al.,
Chalvarjian, A., Rudnicki, E., 1970. Determination of lipid
phosphorus in the nanomolar range. Anal. Biochem. 36, 225–
226.
Coffey, M.D., Cole, R.A., Colles, S.M., Chisolm, G.M., 1995. In
vitro cell injury by oxidized low density lipoprotein involves
lipid hydroperoxide-induced formation of alkoxyl, lipid, and
peroxyl radicals. J. Clin. Invest. 96, 1866–1873.
Feldman, C., Anderson, R., Theron, A.J., Steel, H.C., van
Rensburg, C.E.J., Cole, P.J., Wilson, R., 2001. Vitamin E
attenuates the injurious effects of bioactive phospholipids on
human ciliated epithelium in vitro. Eur. Respir. J. 18, 122–
129.
1
982). The inhibitions of LPC-induced apoptosis and
cell shape change by ␣-T and Chol may be due to
prevention of distortion by membrane stabilization
based on their physicochemical properties and/or di-
rect interaction with LPC molecule. In addition, the
reason why the spherical shape of cells was reversed
in a few hours might be that LPC moved to the inner
leaflet of the plasma membrane and was metabolized
to PC (Besterman and Domanico, 1992).
Fukuzawa, K., Ikeno, H., Tokumura, A., Tsukatani, H., 1979.
Effect of ␣-tocopherol incorporation on glucose permeability
and phase transition of lecithin liposomes. Chem. Phys. Lipids
23, 13–22.
Ghosh, P.K., Vasanji, A., Murugesan, G., Eppell, S.J., Graham,
L.M., Fox, P.L., 2002. Membrane microviscosity regulates
endothelial cell motility. Nat. Cell Biol. 4, 894–900.
Hsieh, C.-C., Yen, M.-H., Liu, H.-W., Lau, Y.-T., 2000.
Lysophosphatidylcholine induces apoptotic and non-apoptotic
death in vascular smooth muscle cells: in comparison with
oxidized LDL. Atherosclerosis 151, 481–491.
Consequently, the apoptosis induced by LPC and
PAF-LL derived from oxLDL in VSMC is suggested
to be mediated by temporary membrane distortion due
to binding of the phospholipids to the cell membrane,
but not through activation of PKC and specific recep-
tors. A common characteristic physicochemical prop-
erty, probably the amphiphilical balance between a
bulky polar head group and a single long hydrocarbon
chain of LPC and PAF-LL would be responsible for
the membrane distortion.
Jalink, K., van Corven, E.J., Moolenaar, W.H., 1990.
Lysophosphatidic acid, but not phosphatidic acid, is a potent
2
+
Ca -mobilizing stimulus for fibroblasts. J. Biol. Chem. 265,
2232–12239.
1
Kagan, V.E., Quinn, P.J., 1998. The interaction of ␣-tocopherol
and homologues with shorter hydrocarbon chains with
phospholipids bilayer dispersions. Eur. J. Biochem. 171, 661–
667.
Kockx, M.M., 1998. Apoptosis in the atherosclerotic plaque:
quantitative and qualitative aspects. Arterioscler Thromb. Vasc.
Biol. 18, 1519–1522.
Kockx, M.M., Knaapen, M.W.M., 2000. The role of apoptosis in
vascular disease. J. Pathol. 190, 267–280.
Acknowledgements
This work was supported in part by a research grant
from the Faculty of Pharmaceutical Sciences, Univer-
sity of Tokushima, Japan.
Kogure, K., Morita, M., Nakashima, S., Hama, S., Tokumura, A.,
Fukuzawa, K., 2001. Superoxide is responsible for apoptosis
in rat vascular smooth muscle cells induced by ␣-tocopheryl
hemisuccinate. Biochim. Biophys. Acta 1528, 25–30.
Kogure, K., Hama, S., Manabe, S., Tokumura, A., Fukuzawa,
K., 2002. High cytotoxicity of ␣-tocopheryl hemisuccinate to
cancer cells is due to failure of their antioxidative defense
systems. Cancer Lett. 186, 151–156.
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