The composition and fluidity of normal and leukaemic or lymphomatous lymphocyte plasma membranes in mouse and man

Sm, Johnson; Robinson, R. D.

doi:10.1016/0005-2736(79)90263-3

Cited by 41 publications

(12 citation statements)

References 39 publications

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“…First, the rate of hydrolysis of susceptible leukocytes is much greater than the rate in susceptible erythrocytes (19,21,23,24). Second, the cell membrane of erythrocytes contain 50-100% more cholesterol (38)(39)(40) than does that of other cells including leukocytes (40)(41)(42). Given the sensitivity of sPLA 2 to membrane structure in general and cholesterol concentration specifically, it is reasonable to hypothesize that membrane cholesterol content might account, at least partially, for the difference in susceptibility of erythrocytes and lymphocytes to hydrolysis by the enzyme.…”

Section: Introductionmentioning

confidence: 99%

Effects of Cholesterol on Physical Properties of Human Erythrocyte Membranes: Impact on Susceptibility to Hydrolysis by Secretory Phospholipase A2

Heiner

Gibbons

Fairbourn

et al. 2008

Biophysical Journal

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The ability of secretory phospholipase A(2) (sPLA(2)) to hydrolyze cell membranes is highly dependent on the physical properties of the membrane. The effects of cholesterol on these properties have been characterized in artificial bilayers and found to alter sPLA(2) activity significantly. It is hypothesized that the natural difference in cholesterol content between erythrocytes and leukocytes is in part responsible for their differing susceptibility to hydrolysis by sPLA(2). To test this hypothesis, defined amounts of cholesterol were removed from erythrocyte membranes using methyl-beta-cyclodextrin. Treatment of cells with methyl-beta-cyclodextrin increased the hydrolysis rate and total substrate hydrolyzed by sPLA(2). In general, this effect of cholesterol removal was more pronounced at higher temperatures. Comparison of the level of membrane order (assessed with the fluorescent probe laurdan) with hydrolysis rate revealed that sPLA(2) activity was greatly enhanced upon significant reductions in lipid order. Additional treatment of the cells with calcium ionophore further enhanced the hydrolysis rate and altered the relationship with membrane order. These data demonstrated that interactions with sPLA(2) observed in artificial bilayers apply to biological membranes. It is also proposed that the high level of cholesterol in erythrocyte membranes is a protective mechanism to guard against hydrolytic enzymes.

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Section: Introductionmentioning

confidence: 99%

Effects of Cholesterol on Physical Properties of Human Erythrocyte Membranes: Impact on Susceptibility to Hydrolysis by Secretory Phospholipase A2

Heiner

Gibbons

Fairbourn

et al. 2008

Biophysical Journal

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“…Firstly, it has been postulated that the membrane uidity plays an important role in selective incorporation of the drugs to cancer cells. Studies on leukemia cells showed that the cancerous membrane is more uid as compared to that of normal cells, which results mainly from decreased total cholesterol and cholesterol--to-phospholipids molar ratio [7] and increased percentage of unsaturated fatty acids acyl chains of the major membrane phospholipids [8]. The same tendency was also observed for other cancerous cell lines (e.g.…”

Section: Introductionmentioning

confidence: 53%

Interactions between Antitumor Alkylphosphocholines and Membrane Sphingolipids in Langmuir Monolayers

2014

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Alkylphosphocholines (APCs) are new generation, highly selective antineoplastic drugs, whose mechanism of action is not fully understood. It is known that in contrast to traditional chemotherapeutics, APCs do not induce cell death by apoptosis or necrosis as a result of DNA damage, but target cellular membranes and aect their biophysical properties. However, it is still unknown which membrane component attracts APC molecules selectively to cancer cells. In order to get insight into this issue, systematic investigations on the interactions between APCs and particular membrane components are highly required. Such experiments can be performed with the Langmuir monolayer technique, serving as a biomembrane model. Because of overexpression of gangliosides in tumor progression and the ability of APCs to insert into membrane rafts, two sphingolipids, i.e. sphingomyelin (SM) and ganglioside GM1 have been examined as potential membrane targets. In this respect, their interactions with three alkylphosphocholines, diering in their hydrophobic part: hexadecylphosphocholine (HePC), octadecylphosphocholine (OcPC) and erucylphosphocholine (ErPC) have been studied and the following systems have been analysed: SM(or GM1)/HePC, SM(or GM1)/OcPC and SM(or GM1)/ErPC. It was found that all the investigated APCs show strong anity to ganglioside in contrast to sphingomyelin. Dierences in interaction of APCs with both investigated sphingolipids were studied based on experimental surface pressure (π) versus mean molecular area (A) isotherms, and analyzed qualitatively (with mean molecular area values) as well as quantitatively (with ∆G exc function). The obtained results have also been analysed taking into consideration geometry of interacting molecules. Our results suggest that gangliosides may be molecular targets for APCs, attracting them to tumor cells. Although the interactions with sphingomyelin were found to be unfavourable, further studies on more complex system, containing APCs mixed with sphingomyelin and cholesterol, are required to better understand the role of lipid rafts in the selectivity of APCs.

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“…(35,36) However, doubt has been cast on the predictability of the location of DPH probe molecules incorporated in membranes. (37) In response to this, DPH derivatives which are covalently bound to phospholipid have been synthesized. These derivatives share the overall fluorescence properties of DPH, but the location and orientation of the probes in the bilayer are much better defined.…”

Section: Photosynthesismentioning

confidence: 99%

Time-Resolved Fluorescence Spectroscopy Using Synchrotron Radiation

Munro

Martin

Topics in Fluorescence Spectroscopy

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The composition and fluidity of normal and leukaemic or lymphomatous lymphocyte plasma membranes in mouse and man

Cited by 41 publications

References 39 publications

Effects of Cholesterol on Physical Properties of Human Erythrocyte Membranes: Impact on Susceptibility to Hydrolysis by Secretory Phospholipase A2

Effects of Cholesterol on Physical Properties of Human Erythrocyte Membranes: Impact on Susceptibility to Hydrolysis by Secretory Phospholipase A2

Interactions between Antitumor Alkylphosphocholines and Membrane Sphingolipids in Langmuir Monolayers

Time-Resolved Fluorescence Spectroscopy Using Synchrotron Radiation

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