Decreased membrane fluidity and beta-adrenergic responsiveness in atherosclerotic quail.
The effects of increased cholesterol on erythrocyte membrane fluidity and beta-adrenergic function were studied in a quail model of atherosclerosis. Birds fed a cholesterol-supplemented diet developed severe atherosclerosis and hypercholesterolemia after 6 wk. This cholesterol-enriched diet led to a markedly elevated serum cholesterol and a 26% increase in the cholesterol-to-phospholipid ratio in erythrocyte membranes. Electron paramagnetic resonance spectra measured with 5- and 12-doxyl-stearic acid spin-label probes were used to estimate the order of quail erythrocyte membranes. Membrane preparations from cholesterol-fed birds were more highly ordered near the membrane leaflet surface, as well as deeper in the membrane interior, compared with controls. beta-Adrenergic receptor stimulation of adenosine 3',5'-cyclic monophosphate accumulation was blunted in erythrocytes from the hypercholesterolemic quail. There was no change in beta-receptor density or affinity in the cholesterol-enriched membranes. These studies demonstrate that cholesterol incorporation into erythrocyte membranes in vivo is associated with decreased membrane fluidity and decreased beta-adrenergic responsiveness. The atherosclerotic quail may serve as a useful model to further probe the sequelae of hypercholesterolemia on the function of integral membrane proteins.
Lurie
K G
KG
Chin
J H
JH
Hoffman
B B
BB
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D003370:Coturnix; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D004910:Erythrocyte Membrane / Q000473:pathology* / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008560:Membrane Fluidity; D008563:Membrane Lipids / Q000378:metabolism; D010743:Phospholipids / Q000097:blood; D011784:Quail; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*
D002791:Cholesterol, Dietary; D008563:Membrane Lipids; D010743:Phospholipids; D011943:Receptors, Adrenergic, beta; D002784:Cholesterol; D000242:Cyclic AMP; D007545:Isoproterenol