Structural and related functional changes in sarcoplasmic reticulum induced by long-chain fatty acids

Munkonge, Felix M.; Stubbs, Christopher D.; Quinn, Peter J.

doi:10.1007/bf00744204

Cited by 6 publications

(2 citation statements)

References 23 publications

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“…Stimulation of the purified enzyme in the latter studies, however, occurred at oleic and linoleic acid concentrations of 10-6-105 M. In the current studies, those fatty acids which were significantly active produced inhibition of enzyme activity at concentrations as low as 10-7-10-8 M. It should be pointed out that in some-reports of Ca2+-ATPase in situ in biological membranes, e.g. striated muscle sarcoplasmic reticulum (Munkonge et al, 1985) or human red cell (Wetzker et al, 1983), oleic acid at 106--10-5 M has previously been found to be inhibitory.…”

Section: Discussioncontrasting

confidence: 46%

Action of long-chain fatty acids in vitro on Ca2+-stimulatable, Mg2+-dependent ATPase activity in human red cell membranes

Davis

Blas

et al. 1987

Biochemical Journal

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Human red cell membrane Ca2+-stimulatable, Mg2+-dependent adenosine triphosphatase (Ca2+-ATPase) activity and its response to thyroid hormone have been studied following exposure of membranes in vitro to specific long-chain fatty acids. Basal enzyme activity (no added thyroid hormone) was significantly decreased by additions of 10(-9)-10(-4) M-stearic (18:0) and oleic (18:1 cis-9) acids. Methyl oleate and elaidic (18:1 trans-9), palmitic (16:0) and lauric (12:0) acids at 10(-6) and 10(-4) M were not inhibitory, nor were arachidonic (20:4) and linolenic (18:3) acids. Myristic acid (14:0) was inhibitory only at 10(-4) M. Thus, chain length of 18 carbon atoms and anionic charge were the principal determinants of inhibitory activity. Introduction of a cis-9 double bond (oleic acid) did not alter the inhibitory activity of the 18-carbon moiety (stearic acid), but the trans-9 elaidic acid did not cause enzyme inhibition. While the predominant effect of fatty acids on erythrocyte Ca2+-ATPase in situ is inhibition of basal activity, elaidic, linoleic (18:2) and palmitoleic (16:1) acids at 10(-6) and 10(-4) M stimulated the enzyme. Methyl elaidate was not stimulatory. These structure-activity relationships differ from those described for fatty acids and purified red cell Ca2+-ATPase reconstituted in liposomes. Thyroid hormone stimulation of Ca2+-ATPase was significantly decreased by stearic and oleic acids (10(-9)-10(-4) M), but also by elaidic, linoleic, palmitoleic and myristic acids. Arachidonic, palmitic and lauric acids were ineffective, as were the methyl esters of oleic and elaidic acids. Thus, inhibition of the iodothyronine effect on Ca2+-ATPase by fatty acids has similar, but not identical, structure-activity relationships to those for basal enzyme activity. To examine mechanisms for these fatty acid effects, we studied the action of oleic and stearic acids on responsiveness of the enzyme to purified calmodulin, the Ca2+-binding activator protein for Ca2+-ATPase. Oleic and stearic acids (10(-9)-10(-4) M) progressively inhibited, but did not abolish, enzyme stimulation by calmodulin (10(-9) M). Double-reciprocal analysis of the effect of oleic acid on calmodulin stimulation indicated noncompetitive inhibition. Addition of calmodulin to membranes in the presence of equimolar oleic acid restored basal enzyme activity. Oleic acid also reduced 125I-calmodulin binding to membranes, but had no effect on the binding of [125I]T4 by ghosts. The mechanism of the decrease by long chain fatty acids of Ca2+-ATPase activity in situ in human red cell ghosts thus is calmodulin-dependent and involves reduction in membrane binding of calmodulin.

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Section: Discussioncontrasting

confidence: 46%

Action of long-chain fatty acids in vitro on Ca2+-stimulatable, Mg2+-dependent ATPase activity in human red cell membranes

Davis

Blas

et al. 1987

Biochemical Journal

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“…Compounds such as dansyl propranolol (Lee et al, 1983) and fatty acids (Froud et al, 1986b;Munkonge et al, 1985;Simmonds et al, 1982) can cause inhibition at high concentrations. At lower concentrations, however, oleic acid has been found to stimulate ATPase activity; the effect being particularly marked for the ATPase reconstituted into bilayers of phospholipids with short fatty acyl chains, such as dimyristoleoylphosphatidylcholine (DMPC, C 1 4 ) (Froud et al, 19866).…”

Section: Introductionmentioning

confidence: 99%

The effects of oleic acid on the activity of the reconstituted Ca2+,Mg2+-ATPase

Michelangeli

Rooney

Lee

1988

Biochemical Society Transactions

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625th MEETING, LONDON 347 Table 1. Effect of lipid-to-protein-ratio on the fluorescence properties of reconstituted Ca ?+, Mg' + -A Tl'ase ATPase was labelled and reconstituted as described in the text. Fluorescence quenching is expressed as F/F,,, where F and 6, are the fluorescence intensities for the donor in the presence and absence of acceptor, respectively. The buffer was 40 mM-Hepes/ KOH, 0 . 1 M-KCI, 5 mM-MgSO,, 0.1 mM-EGTA, pH 7.0,25"C. F/Fi,* Polarixationt Lipid/protein (mol/mol) DOPC DPPC DOPC DPPC I40 0.70 0.49 0.27 1 0.332 250 0.76 0.59 0.2 I8 0.332 470 0.74 0.49 0.2 I 7 0.334 *Fluorescence excited at 475 nm and detected at 520 nm at an ATP concentration o f 0.6 p~. tFluorescence excited at 450 nm and detected at 520 nm at a molar ratio of FITC/EITC/ATPase of 0 . 2 : 0 . 8 : I at an ATPase concentration o f 0.3 p M .labelling ratio, as expected since energy transfer between FITC groups will increase in efficiency with increasing labelling ratio and energy transfer is a depolarizing event. As shown in Table 1, fluorescence polarization is, however, relatively independent of molar ratio of lipid to ATPase, again arguing against the formation of monomeric ATPase species at high dilutions in lipid. Fluorescence polarization is greater for the ATPase reconstituted into gel phase lipid than in liquid crystalline phase lipid (Table 1 ), presumably reflecting restricted motion for the ATPase in gel phase lipid.The experiments reported here suggest that the ATPase is present in reconstituted systems in oligomeric form, relatively independent of lipid-to-protein ratios. These oligomers are envisaged as dynamic crystalline arrays, continually forming and breaking up within the membrane (Napier et a [.,

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The effect of pH on the phase transition temperature of dipalmitoylphosphatidylcholine-palmitic acid liposomes

Fernández

González-Martı́nez

Calderón

1986

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Structural and related functional changes in sarcoplasmic reticulum induced by long-chain fatty acids

Cited by 6 publications

References 23 publications

Action of long-chain fatty acids in vitro on Ca2+-stimulatable, Mg2+-dependent ATPase activity in human red cell membranes

Action of long-chain fatty acids in vitro on Ca2+-stimulatable, Mg2+-dependent ATPase activity in human red cell membranes

The effects of oleic acid on the activity of the reconstituted Ca2+,Mg2+-ATPase

The effect of pH on the phase transition temperature of dipalmitoylphosphatidylcholine-palmitic acid liposomes

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