Regulation of rabbit erythrocyte Ca(2+)-pump sensitivity to calmodulin in experimental hyperlipidemia.
Intracellular free calcium activity is in part determined by a calmodulin-regulated plasma membrane Ca(2+)-pump. Since changes in Ca2+ permeability have been implicated in atherosclerotic plaque formation, we initiated a lipid hyperalimentation protocol during which we measured various erythrocyte calcium flux parameters and early atheroma development. Adolescent New Zealand White rabbits were fed a diet with 0.5% cholesterol and 2.5% lard over a 3-month period. Plasma cholesterol and triacylglycerols increased on average 18.7- and 13.9-fold respectively, while erythrocyte membrane cholesterol content decreased 18% and total phospholipids by 54%. After 3 months of lipid hyperalimentation, 22% of the aortic arch was covered with large, early-stage, raised atheroma. Basal and calmodulin-activated (Ca2+ + Mg2+)-ATPase activities in erythrocyte membranes increased by 31% and 123%, respectively at 2 months, with a concomitant increase in calmodulin affinity (Km) from 15.6 to 4.2 nM. These differences were transient on account of changes in the control animals which exhibited a slowly developing sensitivity to calmodulin during maturation. Basal Ca2+ transport and passive Ca2+ permeability increased about 7-fold during the hyperlipidemic phase. This suggests that overt hyperlipidemia, leading to atherosclerotic plaque development, alters plasma membrane Ca2+ regulatory mechanisms including passive Ca2+ permeability. The changes in enzymatic function, membrane composition, and Ca2+ permeability seen in this red cell model system may be a reflection of early changes in cells that are directly involved in the development of atherosclerotic plaques.
Raess
B U
BU
Department of Pharmacology, Indiana University School of Medicine, Evansville 47712, USA.
Porro
R F
RF
Tunnicliff
G
G
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000097:blood*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002147:Calmodulin / Q000494:pharmacology*; D002784:Cholesterol / Q000097:blood; D004036:Diet, Atherogenic; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism*; D006949:Hyperlipidemias / Q000097:blood / Q000378:metabolism*; D008297:Male; D008563:Membrane Lipids / Q000032:analysis; D008565:Membrane Proteins / Q000378:metabolism; D010539:Permeability; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits; D014280:Triglycerides / Q000097:blood
D002147:Calmodulin; D008563:Membrane Lipids; D008565:Membrane Proteins; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D002118:Calcium