Changes in the molecular structure of axonal and red blood cell membranes following treatment with phospholipase A<sub>2</sub>

Simpkins, Henry; Tay, S.; Panko, E.

doi:10.1021/bi00795a015

Cited by 37 publications

(7 citation statements)

References 24 publications

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“…are consistent with our previous findings since: 1) phospholipase C is known to produce little perturbation to the lipid bilayer of the membrane [17]; and 2) phospholipase A, while known to cause structural changes in the bilayer [18], probably does not alter its internal dielectric constant. This is supported by previous work which has shown that neither product of hydrolysis, fatty acids or lysolecithin, are removed from the membrane [5,18].…”

Section: Osmium Tetroxide Phospholipases a And Csupporting

confidence: 93%

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Binding of spin-labeled local anesthetics to lobster nerves

1973

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Summary. The hyperfine coupling constant of spin-labeled local anesthetics, 2-(N-methyl N-(2,2,6,6-tetramethylpiperidinooxyl)) ethyl 4-alkoxybenzoates, showed these compounds to partition between the aqueous exterior and the hydrocarbon phase of the membrane. Increased partitioning into the hydrocarbon phase of the membrane was in the order: hexyloxy>butoxy>ethoxy. Since these compounds are known to have different durations of anesthesia in the same order, this suggests that durations of activity and ability to partition into the hydrocarbon region of the membrane are related.Local anesthetics block the action potential of nerve axons by preventing the transient increase in permeability of sodium to the axonal membrane [14,16]. The first step in the production of local anesthesia is believed to be an interaction of the drug with the lipid bilayer [15,19]. Since most local anesthetics are basic tertiary amines with pKa values of 7 to 9, at physiological pH they exist in both charged and uncharged forms. Narahashi [13] and others have shown that the charged form is responsible for nerve block activity and exerts its effect from inside of the membrane. However, whether these compounds are completely buried in the bilayer, partially or completely exposed to the outside, is unknown.A technique which is ideally suited to study these possibilities is that of spin labeling as developed by McConnell and colleagues [10] and Jost et aL [7]. It is based on line shape changes of the electron spin resonance spectrum of the nitroxide free radical. In situations where the radical can tumble unrestricted as in solution, three narrow symmetrical lines result. As the molecular motion of the radical decreases the lines become broad and asymmetrical. In addition, since the spectrum of the nitroxide radical is dependent on the dielectric constant of its solvent environment, it can give information concerning the polarity of its binding site. Although other techniques are more capable of giving quantitative data on binding, such as radioactive labeling, they cannot give information concerning the molecdlar properties of the binding sites.16"

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Section: Osmium Tetroxide Phospholipases a And Csupporting

confidence: 93%

“…This is supported by previous work which has shown that neither product of hydrolysis, fatty acids or lysolecithin, are removed from the membrane [5,18]. Thus, the solvent environment surrounding the spin-labeled local anesthetic should be minimally affected.…”

Section: Osmium Tetroxide Phospholipases a And Csupporting

confidence: 58%

Binding of spin-labeled local anesthetics to lobster nerves

1973

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“…[Model bilayers composed of phosphatidylcholine, however, are more fluid than those of phosphatidylethanolamine (77,78).] Similar methylation reactions in vesicles of hog kidney cortex did not alter the fluorescence polarization of diphenylhexatriene (130), so the fluidity change may be cell-specific or require special conditions. As noted in a prior section, administration to rats of S-adenosyl-L-methionine, the methyl donor for these transmethylations, increased the fluidity of the hepatocyte plasma membranes isolated subsequently (117).…”

Section: Hepatocyte Plasma Membrane Proteins Influence the Membranementioning

confidence: 99%

“…These changes are ascribed to the action of endogenous phospholipase Az, which is well-known to be calcium-sensitive in the millimolar concentration range (1)(2)(3)(4) and to cleave arachidonate, which is located preferentially at the sn-2 position of the phospholipid backbone (128). Treatment of hepatocyte plasma membranes (129), human erythrocyte membranes (130), or lobster axonal membranes (130) with exogenous phospholipase A2 has also been shown to decrease the lipid fluidity. It is proposed, therefore, that one function of phospholipase Az is as a regulator of membrane fluidity.…”

Section: Hepatocyte Plasma Membrane Proteins Influence the Membranementioning

confidence: 99%

Fluidity and Function of Hepatocyte Plasma Membranes

Schachter

1984

Hepatology

232

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LIPID-PROTEIN INTERACTIONS INMEMBRANES This review considers the basic biological problem of how the lipids and proteins of hepatocyte plasma membranes interact to mediate and regulate membrane functions. The following general hypothesis, which is applicable to all natural membranes, is a suitable framework for the discussion, inasmuch as it rests on a considerable body of experimental evidence. MEMBRANE MEMBRANE PROTEINS influence LIPIDS(and the specific -(and their functions properties) mediated by them)The influence of endogenous membrane enzymes, such as phospholipases (1-4), methyltransferases (5, 6), and fatty acid desaturases (7-lo), on membrane phospholipids is well-documented. Such reactions can alter the composition and properties of the bilayer lipid environment and thereby affect the functions of those membrane proteins ("integral" proteins) which are embedded in or traverse the lipid core of the membrane. A key property of the lipids, in this regard, is the "fluidity", or general motional freedom of the lipid molecules. A growing body of evidence indicates that the fluidity of the lipid environment influences the activity of such physiologically important membrane enzymes as the (Na+ + Ka+)-dependent adenosine triphosphatase (11-16) and hormoneresponsive adenylate cyclase (16-20). The fluidity also modulates transmembrane transport processes (21-24) and is a determinant of the passive permeability characteristic of a given bilayer (23, 25-28).The interactions of membrane proteins and lipids implicit in the general hypothesis above could provide regulatory loops for the control of important cell functions. For example, recent evidence indicates that calcium ion

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“…and were the 7-nitroxide (n = 10, m= 5) and the 5-nitroxide (n = 12, m = 3). The preparation of these labels has already been described (Simpkins et al, 1971b) except that the 5-oxo acid was prepared as described by Jost et al (1971). The labelling of the membranes with the protein and fatty acid labels was performed as described by Simpkins et al (1971b) except that the buffer employed was 0.5mM-CaC12-1 mM-tris-HCl buffer, pH7.5, and the washing was performed by centrifugation of the membrane fractions at 150000g.…”

Section: Spin-labelling Studiesmentioning

confidence: 99%

A comparative study of the molecular structures of the plasma membranes and the smooth and the rough endoplasmic-reticulum membranes from rat liver

Morin

Tay

Simpkins

1972

Biochemical Journal

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Plasma-membrane as well as smooth-, rough- and degranulated-endoplasmic-reticulum-membrane fractions were isolated from the microsomal pellet of rat liver. The purity of these fractions, as determined by marker-enzyme activities, electron microscopy, cholesterol content and RNA content, was found to be adequate for a comparative structural study. Major differences in lipid and protein composition were found to exist between the plasma membrane and the endoplasmic reticulum, but not between the smooth and the rough fractions of the endoplasmic reticulum. Differences in the location of membrane protein thiol groups and the mobility of the membrane phospholipids were observed between the plasma membranes and the endoplasmic reticulum, and these could be explained by differences in protein and lipid composition. However, by employing fluorescence and spin-labelling techniques structural changes were also observed between the smooth and the rough endoplasmic-reticulum fractions. These results suggest that the structural heterogeneity existing between the two latter membrane fractions occurs near or on their membrane surfaces and is not due to the greater number of ribosomes bound to the rough endoplasmic-reticulum fraction.

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Changes in the molecular structure of axonal and red blood cell membranes following treatment with phospholipase A₂

Cited by 37 publications

References 24 publications

Binding of spin-labeled local anesthetics to lobster nerves

Binding of spin-labeled local anesthetics to lobster nerves

Fluidity and Function of Hepatocyte Plasma Membranes

A comparative study of the molecular structures of the plasma membranes and the smooth and the rough endoplasmic-reticulum membranes from rat liver

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Changes in the molecular structure of axonal and red blood cell membranes following treatment with phospholipase A2

Cited by 37 publications

References 24 publications

Binding of spin-labeled local anesthetics to lobster nerves

Binding of spin-labeled local anesthetics to lobster nerves

Fluidity and Function of Hepatocyte Plasma Membranes

A comparative study of the molecular structures of the plasma membranes and the smooth and the rough endoplasmic-reticulum membranes from rat liver

Contact Info

Product

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Changes in the molecular structure of axonal and red blood cell membranes following treatment with phospholipase A₂