Function and metabolism
which had incorporated t {
3 H]-alkyl-Gro. Our data showed only a basal
alkyl-acyl-Gro amount after 2 min-stimulation by PMA, while A23187
could induce a significant raise in alkyl-acyl-Gro production from
membrane alkyl-PL. These results might explain the endothelial permeability inhibition. Our hypothesis is that basal level of alkyl-acylGro is sufficient for inhibiting PKC and therefore prevent both phospholipase C or D stimulation and permeability raise after PMA treatment,
while the calcium raise induced by A23187 treatment activated directly
phospholipase C and/or D, resulting in the increased conversion of
alkyl-PC to alkyl-acyl-Gro which further inhibited PKC and brought
endothelial permeability below control values. This hypothesis remains
to be further investigated.
In summary, this study demonstrated that alkyl-Gro incorporation into
membrane PL of endothelial cells results in inhibition of endothelial
monolayer raise in permeability after cell stimulation. Our data suggest
that this effect occurs through PKC mhibition, possibly by production
of alkyl-acyl-Gro. These properties of alkyl-Gro might present interest
in various pathophysiological conditions.
Bibliographic references
Bligh E.G., Dyer W.J., 1959. A rapid method of total lipid extraction
and purification. Can. J. Biochem. Physiol., 37, 91 1-917.
Brohult A., 1963. Alkoxyglycerols and their use in radiation treatment. Acta Radiol., Suppl., 223, 1-99.
Brohult A., Brohult J., Brohult S., Joelsson I., 1977. Effect of alkoxyglycerols on the frequency of injuries following radiation therapy
for carcinoma of the uterine cervix. Acta Obstet. Gynecol. Scand.,
36, 441-448.
Brohult A., Brohult J., Brohult S., 1978. Regression of tumour growth
after administration ofalkoxyglycerols. Acta Obstet. Gynecol. Scand.,
37, 79-83.
Daniel L.W., Small (G.W., Schmitt J.D., Marasco C.J., Ishacj K., Piantadosi C., 1988. Alkyl-linked diglycerides inhibit protein kinase
C activation by diacylglycerols. Biochem. Biophys. Res. Commun.,
151, 291-297.
Exton J.H., 1994. Phosphatidylcholine breakdown and signal transduction. Biochim. Biophys. Acta, 1212, 26-42.
Hichami A., Duroudier V., Leblais V., Vernhet L., Le Goffic E, Ninio E.,
Legrand A., 1997. Modulation of platelet-activating factor production by incorporation of naturally occurring 1-O-alkylglycerols in
phospholipids of human leukemic monocyte-like THP-1 cells. Eur.
J. Biochem., 250, 242-248.
Hug H., Sarre T.F., 1993. Protein kinase C isoenzymes: divergence in
signal transduction? Biochem. J., 291,329-34.3.
153
which had incorporated t {
3 H]-alkyl-Gro. Our data showed only a basal
alkyl-acyl-Gro amount after 2 min-stimulation by PMA, while A23187
could induce a significant raise in alkyl-acyl-Gro production from
membrane alkyl-PL. These results might explain the endothelial permeability inhibition. Our hypothesis is that basal level of alkyl-acylGro is sufficient for inhibiting PKC and therefore prevent both phospholipase C or D stimulation and permeability raise after PMA treatment,
while the calcium raise induced by A23187 treatment activated directly
phospholipase C and/or D, resulting in the increased conversion of
alkyl-PC to alkyl-acyl-Gro which further inhibited PKC and brought
endothelial permeability below control values. This hypothesis remains
to be further investigated.
In summary, this study demonstrated that alkyl-Gro incorporation into
membrane PL of endothelial cells results in inhibition of endothelial
monolayer raise in permeability after cell stimulation. Our data suggest
that this effect occurs through PKC mhibition, possibly by production
of alkyl-acyl-Gro. These properties of alkyl-Gro might present interest
in various pathophysiological conditions.
Bibliographic references
Bligh E.G., Dyer W.J., 1959. A rapid method of total lipid extraction
and purification. Can. J. Biochem. Physiol., 37, 91 1-917.
Brohult A., 1963. Alkoxyglycerols and their use in radiation treatment. Acta Radiol., Suppl., 223, 1-99.
Brohult A., Brohult J., Brohult S., Joelsson I., 1977. Effect of alkoxyglycerols on the frequency of injuries following radiation therapy
for carcinoma of the uterine cervix. Acta Obstet. Gynecol. Scand.,
36, 441-448.
Brohult A., Brohult J., Brohult S., 1978. Regression of tumour growth
after administration ofalkoxyglycerols. Acta Obstet. Gynecol. Scand.,
37, 79-83.
Daniel L.W., Small (G.W., Schmitt J.D., Marasco C.J., Ishacj K., Piantadosi C., 1988. Alkyl-linked diglycerides inhibit protein kinase
C activation by diacylglycerols. Biochem. Biophys. Res. Commun.,
151, 291-297.
Exton J.H., 1994. Phosphatidylcholine breakdown and signal transduction. Biochim. Biophys. Acta, 1212, 26-42.
Hichami A., Duroudier V., Leblais V., Vernhet L., Le Goffic E, Ninio E.,
Legrand A., 1997. Modulation of platelet-activating factor production by incorporation of naturally occurring 1-O-alkylglycerols in
phospholipids of human leukemic monocyte-like THP-1 cells. Eur.
J. Biochem., 250, 242-248.
Hug H., Sarre T.F., 1993. Protein kinase C isoenzymes: divergence in
signal transduction? Biochem. J., 291,329-34.3.
153