Effect of dexamethasone on the fatty acid composition of total liver microsomal lipids and phosphatidylcholine molecular species.
Dexamethasone depresses delta6 and delta5 and increases delta9 desaturase and synthase activities. Therefore, we investigated the effect on the fatty acid composition of microsomal liver lipids and phosphatidylcholine (PtdCho) molecular species. After 15 d of treatment we found a notable decrease in arachidonic acid, a small decrease in stearic acid, and increases of linoleic, oleic, palmitoleic, and palmitic acids in liver microsomal total lipids and PtdCho. The study of the distribution of the PtdCho molecular species indicated that 18:0/20:4n-6, 16:0/20:4n-6, and 16:0/18:2n-6 predominated in the control animals. Dexamethasone, as expected because of its depressing effect on arachidonic acid synthesis and activation of oleic and palmitic acid synthesis, evoked a very significant decrease in 18:0/20:4n-6 PtdCho (P<0.001) and an important increase in 16:0/18:2n-6. The invariability of 16:0/20:4n-6 PtdCho could be related to the antagonistic effect of arachidonic and palmitic acid synthesis. PtdCho species containing oleic acid were not significant. The bulk fluidity and dynamic properties of the microsomal lipid bilayer measured by fluorometry using the probes 1,6-diphenyl-1,3,5-hexatriene and 4-trimethylammonium-phenyl-6-phenyl-1,3,5-hexatriene showed no significant modification, probably owing to a compensatory effect of the different molecular species, but changes of particular domains not detected by this technique are possible. However, the extremely sensitive Laurdan detected increased lipid packing in the less-fluid domains of the polar-nonpolar interphase of the bilayer, possibly evoked by the change of molecular species and cholesterol/phospholipid ratio. The most important effect found is the decrease of arachidonic acid pools in liver phospholipids as one of the corresponding causes of dexamethasone-dependent pharmacological effects.
Brenner
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RR
Instituto de Investigaciones Bioquímicas de La Plata (INIBIOLP), CONICET-UNLP, Facultad de Ciencias Médicas, Argentina. rbrenner@atlas.med.unlp.edu.ar
Ayala
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S
Garda
H A
HA
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D044943:Fatty Acid Desaturases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005227:Fatty Acids / Q000032:analysis*; D005938:Glucocorticoids / Q000494:pharmacology; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D005227:Fatty Acids; D005938:Glucocorticoids; D008055:Lipids; D010713:Phosphatidylcholines; D003907:Dexamethasone; D044943:Fatty Acid Desaturases