Chlorpromazine inhibits vesiculation, alters phosphoinositide turnover and changes deformability of ATP-depleted RBCs

Bütikofer, Peter; Lin, ZW; Kuypers, FA; Scott, Alexander P.; Xu, Caixia; Wagner, G.; Chiu, DT; Lubin, Bertram H.

doi:10.1182/blood.v73.6.1699.1699

Cited by 50 publications

(10 citation statements)

References 34 publications

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“…Trypanosome lipids were extracted with chloroform : methanol (2:1, by volume) as described before (Signorell et al, 2008a). Phospholipids were separated by two-dimensional TLC using solvent system 1 (chloroform : methanol : ammonia : water, 90:74:12:8, by volume) for the first and solvent system 2 (chlorofom : methanol : acetone : acetic acid : water, 40:15:15:12:8, by volume) for the second dimension (Bütikofer et al, 1989). On each plate, appropriate lipid standards were run alongside the samples to be analysed.…”

Section: Lipid Extraction and Phosphorous Determinationmentioning

confidence: 99%

Perturbation of phosphatidylethanolamine synthesis affects mitochondrial morphology and cell‐cycle progression in procyclic‐form Trypanosoma brucei

Signorell

Gluenz

Rettig

et al. 2009

Molecular Microbiology

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SummaryPhosphatidylethanolamine (PE) and phosphatidylcholine (PC) are the two major constituents of eukaryotic cell membranes. In the protist Trypanosoma brucei, PE and PC are synthesized exclusively via the Kennedy pathway. To determine which organelles or processes are most sensitive to a disruption of normal phospholipid levels, the cellular consequences of a decrease in the levels of PE or PC, respectively, were studied following RNAi knockdown of four enzymes of the Kennedy pathway. RNAi against ethanolamine-phosphate cytidylyltransferase (ET) disrupted mitochondrial morphology and ultrastructure. Electron microscopy revealed alterations of inner mitochondrial membrane morphology, defined by a loss of disk-like cristae. Despite the structural changes in the mitochondrion, the cells maintained oxidative phosphorylation. Our results indicate that the inner membrane morphology of T. brucei procyclic forms is highly sensitive to a decrease of PE levels, as a change in the ultrastructure of the mitochondrion is the earliest phenotype observed after RNAi knock-down of ET. Interference with phospholipid synthesis also impaired normal cell-cycle progression. ET RNAi led to an accumulation of multinucleate cells. In contrast, RNAi against choline-/ethanolamine phosphotransferase, which affected PC as well as PE levels, caused a cell division phenotype characterized by non-division of the nucleus and production of zoids.

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Section: Lipid Extraction and Phosphorous Determinationmentioning

confidence: 99%

Perturbation of phosphatidylethanolamine synthesis affects mitochondrial morphology and cell‐cycle progression in procyclic‐form Trypanosoma brucei

Signorell

Gluenz

Rettig

et al. 2009

Molecular Microbiology

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“…139 Vesiculation is important in a variety of hemolytic disorders. Butikofer and colleagues 140 pointed out that when RBCs are ATP-depleted, the echinocytosis that occurs may be related to the conversion of PIP 2 to phosphatidylinositol leading to spiculation (echinocytosis) of the membrane. They found that this could be inhibited by the insertion of chlorpromazine into the lipid layer of the corpuscular membrane.…”

Section: Rbc Vesiculation In Diseasementioning

confidence: 99%

The how and why of exocytic vesicles

Greenwalt¹

2005

Transfusion

183

155

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The purpose of this review is to draw the attention of general readers to the importance of cellular exocytic vesiculation as a normal mechanism of development and subsequent adjustment to changing conditions, focusing on red cell (RBC) vesiculation. Recent studies have emphasized the possible role of these microparticles as diagnostic and investigative tools. RBCs lose membrane, both in vivo and during ex vivo storage, by the blebbing of microvesicles from the tips of echinocytic spicules. Microvesicles shed by RBCs in vivo are rapidly removed by the reticuloendothelial system. During storage, this loss of membrane contributes to the storage lesion and the accumulation of the microvesicles are believed to be thrombogenic and thus to be clinically important.

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“…† P р 0 . 01 compared with controls.man, 1981;Bü tikofer et al, 1989), which may point a way for the development of new therapeutic strategies.…”

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confidence: 99%

The anti‐neoplastic drug 5‐fluorouracil produces echinocytosis and affects blood rheology

Baerlocher¹,

Beer²,

Owen³

et al. 1997

Br J Haematol

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Summary. The anti-neoplastic agent 5-fluorouracil (5-FU) in high therapeutic doses can induce angina pectoris and myocardial infarction. The pathophysiological mechanism of this side-effect has not yet been elucidated. We analysed the influence of 5-FU on blood rheology in vitro. Whole blood, blood cell suspensions and plasma were incubated with increasing concentrations of 5-FU (final concentrations 0, 0 . 08, 0 . 4, 2, 10 and 25 mg/ml 5-FU) at 37ЊC. Erythrocyte morphology was analysed after fixation with glutaraldehyde. Viscosity was measured at high and low shear rates (94 and 0 . 1 s -1 ). Erythrocyte aggregation and the cell transit times of erythrocytes through 5 mm pores and polymorphonuclear leucocytes through 8 mm pores were determined. 5-FU induced a dose-dependent formation of echinocytes within minutes and was reversible upon removal of 5-FU, which reflected a preferential intercalation of the drug in the outer hemileaflet of the cell membrane. High shear blood viscosity was increased at the highest 5-FU concentration (148 Ϯ 12%), and at low shear rate a dose-dependent decrease was found (0 mg/ml: 100%, 0 . 08 mg/ml: 87 Ϯ 10%, 0 . 4 mg/ml: 80 Ϯ 19%, 2 mg/ml: 70 Ϯ 15%, 10 mg/ml: 40 Ϯ 19%, 25 mg/ml: 33 Ϯ 5%). Erythrocyte aggregation was decreased by the 5-FU-induced echinocytosis. The transit time of erythrocytes through narrow pores was increased in a dose-dependent manner by 5-FU, whereas the transit time of polymorphonuclear leucocytes was initially decreased at 10 mg/ml and returned to control after 60 min incubation. We conclude that 5-FU interacts with the cell membrane, induces echinocytosis and vesiculation and affects blood rheology in several ways which may contribute to cardiovascular complications.

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Chlorpromazine inhibits vesiculation, alters phosphoinositide turnover and changes deformability of ATP-depleted RBCs

Cited by 50 publications

References 34 publications

Perturbation of phosphatidylethanolamine synthesis affects mitochondrial morphology and cell‐cycle progression in procyclic‐form Trypanosoma brucei

Perturbation of phosphatidylethanolamine synthesis affects mitochondrial morphology and cell‐cycle progression in procyclic‐form Trypanosoma brucei

The how and why of exocytic vesicles

The anti‐neoplastic drug 5‐fluorouracil produces echinocytosis and affects blood rheology

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