Role of the bilayer in the shape of the isolated erythrocyte membrane

Lange, Yvonne; Gough, Alice; Steck, Theodore L.

doi:10.1007/bf01872271

Cited by 51 publications

(41 citation statements)

References 37 publications

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“…12,27) Meanwhile, the previous reports demonstrated that changes in the ratio of cholesterol/phospholipids or distribution of membrane components affect membrane deformability. [30][31][32] As a result, we clarified here that M-b-CyD and DM-b-CyD significantly extracted cholesterol rather than phospholipids from RRBC membranes to the supernatant (Fig. 3), resulting in inhomogeneous rigidity in RRBC membranes followed by RRBC deformation.…”

Section: Discussionmentioning

confidence: 71%

Involvement of Lipid Rafts of Rabbit Red Blood Cells in Morphological Changes Induced by Methylated .BETA.-Cyclodextrins

Motoyama

Toyodome

Onodera

et al. 2009

Biological & Pharmaceutical Bulletin

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One of the most substantial requirements for drug and drug carriers is to have either no or low levels of intrinsic cytotoxicity. To evaluate cytotoxicity, the cell culture system has been frequently used, e.g. a dye exclusion assay, 51 Cr release assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) assay and 3 H-thymidine uptake assay. Studies with isolated red blood cells (RBC), which have no nucleus, mitochondria, endoplasmic reticulum, or other organelles, may provide simple and reliable information to classify the drug and drug carriers according to their cytotoxicity because the interaction of drugs and drug carriers with plasma membranes must be the initial step of cell damage. 1)Lipid rafts are dynamic assemblies of proteins and lipids that float freely within the liquid-disordered bilayer of cellular membranes but can also cluster to form larger, ordered platforms.2-4) Lipid rafts are mainly composed of cholesterol and sphingolipids such as sphingomyelin in the cell membranes. 5,6) Recently, it is thought that lipid rafts on cell membranes have heterogeneity such as cholesterol-rich microdomains and sphingolipids-rich microdomains. [7][8][9][10] In addition, lipid rafts contain proteins involved in the regulation of actin rearrangement, and the actin cytoskeleton has crucial role in inducing and sustaining rafts polarization in cells. 9)Cyclodextrins (CyDs) and their hydrophilic derivatives form inclusion complexes with hydrophobic molecules. CyDs can improve the solubility, dissolution rate and bioavailability of the drugs, and so the widespread use of CyDs is well known in the pharmaceutical field.12,13) CyDs have been reported to interact with cell membrane constituents such as cholesterol and phospholipids, resulting in the induction of hemolysis of human and rabbit RBC. [14][15][16] Additionally, methyl-b-cyclodextrin (M-b-CyD) is acknowledged to disrupt the structures of lipid rafts and caveolae, 17,18) which are lipid microdomains formed by lateral assemblies of cholesterol and sphingolipids in the cell membrane, through extraction of cholesterol from the microdomains. 19) We previously reported that a-CyD, b-CyD and g-CyD, which are composed of 6, 7 and 8 glucose units, induce morphological changes in erythrocytes from discocyte to stomatocyte and hemolysis at higher concentrations.20) The magnitude of hemolytic activity of the CyDs was reported to increase in the order of g-CyDϽa-CyDϽb-CyD. 14,20) Recently, various hydrophilic CyD derivatives have been developed to improve aqueous solubility and the complexation ability of the CyDs. Of various hydrophilic CyD derivatives, hydroxypropylated CyDs, sulfobutyl ether CyDs and branched CyDs have been demonstrated to have lesser hemolytic activities than the CyDs.21) More recently, we revealed that 2,6-di-O-methyl-a-CyD (DM-a-CyD) has higher hemolytic activity and morphological change ability from discocyte to stomatocyte than a-CyD and 2-hydroxypropyla-CyD (HP-a-CyD), probably through the ext...

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Section: Discussionmentioning

confidence: 71%

Involvement of Lipid Rafts of Rabbit Red Blood Cells in Morphological Changes Induced by Methylated .BETA.-Cyclodextrins

Motoyama

Toyodome

Onodera

et al. 2009

Biological & Pharmaceutical Bulletin

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“…The inaccessibility ofa fraction ofthe PPI to their kinases can explain also why, in cholesterol-depleted relative to control erythrocytes, 32p incorporation into PPI was reduced without changes in their concentration or the specific activity of ATP (Giraud et al, 1984). The possibility that the membrane cholesterol content can influence the phospholipid organization has been suggested previously in different situations: shape change in erythrocytes (Lange et al, 1982), thrombin-induced changes in platelet phospholipid metabolism (Kramer et al, 1982), adenylate cyclase activity modulation in hepatocytes (Whetton et al, 1983), phosphatidylcholine and phosphatidylethanolamine hydrolysis rate by phospholipase A2 in fibroblasts (Fisher et al, 1983).…”

Section: Vol 234mentioning

confidence: 80%

Phosphoinositide reorganization in human erythrocyte membrane upon cholesterol depletion

M'Zali¹,

Giraud²

1986

Biochemical Journal

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The effect of cholesterol depletion on the activity of phosphatidylinositol/phosphatidylinositol 4-phosphate and diacylglycerol kinases and polyphosphoinositide phosphodiesterase has been studied in isolated membranes of human normal and cholesterol-depleted erythrocytes. Polyphosphoinositide synthesis (phosphatidylinositol/phosphatidylinositol 4-phosphate kinase activities) were found to depend on the permeability and sidedness characteristics of the membrane vesicles, which could limit the accessibility of ATP for the enzymes. When measured under proper conditions, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate synthesis were decreased in cholesterol-depleted membranes as compared with control membranes. The same level of synthesis could be obtained in both membranes by the addition ofphosphatidylinositol (and Triton X-100) or ofphosphatidylinositol 4-phosphate. Phosphatidic acid synthesis (diacylglycerol kinase activity) was also decreased in cholesterol-depleted membranes as compared with control membranes when measured in the presence of Ca2+. Addition of diolein (and Triton X-100) caused a large increase in phosphatidic acid synthesis which reached approximately the same level in both membranes. This showed that the apparent inhibition of polyphosphoinositide and phosphatidic acid synthesis was not due to a loss or to an inactivation of the kinases. Ca2+-activated polyphosphoinositide phosphodiesterase promoted the hydrolysis of 65-70% of the polyphosphoinositides in control and of only

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“…We conclude that echinocytogenesis involves the occupation of binding sites on the cell surface by abnormal HDL. How this causes the imbalance of area between the membrane leaflets implied by echinocytosis (22,(37)(38)(39) (45) considered that only in patients with spur cells did morphologic alterations lead to the premature removal of cells (though their scanning electron micrograph of a spur cell showed an echinocyte). The hemoglo-bin levels in our patients did not correlate closely with the number of echinocytes in their blood.…”

Section: Discussionmentioning

confidence: 99%

Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins.

Owen¹,

Brown²,

Harry³

et al. 1985

J. Clin. Invest.

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Echinocytes were frequently found in patients with liver disease when their blood was examined in wet films, but rarely detected in dried, stained smears. When normal erythrocytes (discocytes)were incubated with physiologic concentrations of the abnormal high density lipoproteins (HDL) from some jaundiced patients, echinocytosis developed within seconds. Other plasma fractions were not echinocytogenic. There was a close correlation between the number of echinocytes found in vivo and the ability of the corresponding HDL to induce discocyte-echinocyte transformation. On incubation with normal HDL, echinocytes generated in vitro rapidly reverted to a normal shape, and echinocytes from patients showed a similar trend. Echinocytosis occurred without change in membrane cholesterol content, as did its reversal, and was not caused by membrane uptake of lysolecithin or bile acids. Abnormal, echinocytogenic HDL showed saturable binding to -5,000 sites per normal erythrocyte with an association constant of 108 M-'. Nonechinocytogenic patient HDL and normal HDL showed only nonsaturable binding. Several minor components of electrophoretically separated erythrocyte membrane proteins bound the abnormal HDL; pretreatment of the cells with trypsin or pronase reduced or eliminated binding. Echinocytosis by abnormal HDL required receptor occupancy, rather than transfer of constituents to or from the membrane, because cells reversibly prefixed in the discoid shape by wheat germ agglutinin, and then exposed to abnormal HDL, did not become echinocytes when the HDL and lectin were successively removed. Binding did not cause dephosphorylation of spectrin. We conclude that the echinocytes of liver disease are generated from discocytes by abnormal HDL, and we infer that the shape change is mediated by cell-surface receptors for abnormal HDL molecules.

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Role of the bilayer in the shape of the isolated erythrocyte membrane

Cited by 51 publications

References 37 publications

Involvement of Lipid Rafts of Rabbit Red Blood Cells in Morphological Changes Induced by Methylated .BETA.-Cyclodextrins

Involvement of Lipid Rafts of Rabbit Red Blood Cells in Morphological Changes Induced by Methylated .BETA.-Cyclodextrins

Phosphoinositide reorganization in human erythrocyte membrane upon cholesterol depletion

Erythrocyte echinocytosis in liver disease. Role of abnormal plasma high density lipoproteins.

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