Dithiothreitol stimulates the activity of the plasma membrane aminophospholipid translocator

Truong, Hoai-Thu N.; Daleke, David L.; Huestis, Wray H.

doi:10.1016/0005-2736(93)90121-f

Cited by 11 publications

(4 citation statements)

References 29 publications

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“…The modulation of erythrocyte physiological events by dithiothreitol is becoming increasingly documented [34,38,39] and ongoing studies from our unit are disclosing its thiol-reducing property to be the major role in erythrocyte function.…”

Section: Modulation Of Erythrocyte Properties By Dttmentioning

confidence: 99%

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Dithiothreitol revisited in red cells: A new head for an old hat

Almeida

Saldanha

2010

Clinical Hemorheology and Microcirculation

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In the present article the authors make an approach over the applications of dithiothreitol (DTT) in its different clinicallaboratory, potential and up-to-date sources. Dithiothreitol is a chemical reagent with a wide actuation spectrum not only from a laboratorial view but also from a therapeutic standpoint, more clinical and practical. DTT (i) is frequently used in a variety of experiences that involve proteins or peptides, protecting sulfhydryl groups from oxidation and reducing disulfide bonds between cysteines; (ii) is also used in the study of disulfide exchange reactions of protein disulfides; (iii) is able to keep glutathione in the reduced state; (iv) acts as an "antidote" enabling the activity of detoxification systems; (v) participates in cellular mechanisms such as vesiculation, cell morphology, signal transduction pathways (hormone-'like' role), etc.; (vi) can be used in the treatment approach of diseases like cystinosis or medical conditions resulting from ion or metal toxicity. In erythrocytes, there's literature pointing that DTT may trigger changes on the normal discoid shape following metabolic depletion, and additionally modulate the exovesiculation kinetics as demonstrated by us. The present article dissects in detail recent findings in our Unit concerning the DTT influence on human erythrocytes.

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Section: Modulation Of Erythrocyte Properties By Dttmentioning

confidence: 99%

“…In DTT-treated cells, this morphology deformation goes further until the final form is a stomatocyte. This counter-regulation is the result of exaggerated stimulation of the plasma membrane aminophospholipid translocator by DTT [38,39].…”

Section: Modulation Of Erythrocyte Properties By Dttmentioning

confidence: 99%

Dithiothreitol revisited in red cells: A new head for an old hat

Almeida

Saldanha

2010

Clinical Hemorheology and Microcirculation

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“…3D). APT contains Cys residues sensitive to redox and electrophilic agents causing loss of enzymatic activity (7,41). To determine the extent to which anti-Fas-induced APT inactivation was due to disulfide formation, we used a…”

Section: Effects Of Vitamin E On Anti-fas-induced Apoptosismentioning

confidence: 99%

Vitamin E Inhibits Anti-Fas-Induced Phosphatidylserine Oxidation but Does Not Affect Its Externalization During Apoptosis in Jurkat T Cells and Their Phagocytosis by J774A.1 Macrophages

Serinkan

Tyurina²,

Babu³

et al. 2004

Antioxidants & Redox Signaling

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Apoptosis and phagocytosis of apoptotic cells provide for effective and harmless clearance of unwanted or damaged cells in the body. Preferential oxidation of one particular class of phospholipids, phosphatidylserine (PS), is a typical trait of both oxidant- and nonoxidant-induced apoptosis. PS oxidation is likely to play an important role in phagocytosis either by affecting PS externalization acting as an "eat me" signal or by more effective recognition of apoptotic cells by macrophage receptors. This implies that antioxidants effective in inhibiting PS oxidation may affect PS externalization and/or effective removal of apoptotic cells. Therefore, it is essential to determine whether vitamin E, the major lipid-soluble antioxidant of membranes, inhibits PS oxidation, and hence blocks apoptosis/phagocytosis. To test this, we studied the effects of vitamin E on PS oxidation and signaling using a model of anti-Fas-triggered apoptosis in Jurkat T cells. We found that incubation of cells with vitamin E (0.25-50 micro M) resulted in its integration into cells to reach physiologically relevant concentrations. Using labeling of cell phospholipids with oxidation-sensitive and fluorescent cis-parinaric acid (PnA), we found that anti-Fas exposure caused significant and selective oxidation of PnA-PS in Jurkat T cells (22 +/- 2.1% of its content in nonexposed cells). Vitamin E protected PnA-PS against oxidation in a concentration-dependent way such that at 25 micro M and 50 micro M, a complete inhibition of anti-Fas-induced PS oxidation was achieved. At all concentrations used, vitamin E had no effect on either biomarkers of anti-Fas-induced apoptosis (PS externalization, nuclear fragmentation) or phagocytosis of anti-Fas-induced apoptotic cells by J774A.1 macrophages. We conclude that vitamin E does not significantly interfere with extrinsic (death receptor-triggered) pathways of apoptosis and does not affect phagocytosis of anti-Fas-triggered apoptotic cells.

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“…It is used in a widening array of studies involving proteins/peptides to protect sylfhydryl (-SH) groups from oxidation and to reduce disulfide bonds between cysteines [16,17]. Due to these properties, DTT is also used in the study of disulfide exchange reactions of protein disulfides [18]; glutathione reduction, enabling cellular protection [19]; the activity of detoxification systems especially of toxic drugs to their non-toxic compounds [20,21]; vesiculation, cell morphology, and modulation of cell ion currents [22,23]. Given that DTT properties go beyond its effects on the cellular redox thiol status, it can interact with proteins in the absence of cysteine residues and, for example, yield zinc-DTT complexes which prevent this metal toxicity [24].…”

Section: Introductionmentioning

confidence: 99%

Modulation of hemorheological parameters by the erythrocyte redox thiol status

Almeida

Carvalho

Freitas

et al. 2008

Clinical Hemorheology and Microcirculation

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Background: There is growing knowledge about the association between hemorheological blood disorders and compromised microcirculation in erythrocyte abnormalities. Effects of the non-neuronal cholinergic elements, especially acetylcholinesterase, on the erythrocyte hemorheological parameters were characterized in the past. However, alterations of these parameters have not been studied under the influence of the cellular redox thiol status.Methods: Aliquots of venous blood from ten healthy male subjects were incubated in vitro with increasing concentrations of a thiol reducer agent (dithiothreitol 1, 10, 50 µM final concentrations) in the presence and absence of acetylcholinesterase substrate (acetylcholine) or inhibitor (velnacrine maleate). The following parameters were determined in all blood samples aliquots: erythrocyte aggregation, erythrocyte deformability and lipid membrane fluidity. Blood smears were performed.Results: Dithiothreitol induces no significant changes on the hemorheological behaviour of human red cells. Upon intracellular thiol stimulation, the presence of AChE effectors (either acetylcholine or velnacrine) decreases erythrocyte aggregation and elongation indexes.Conclusion: The addition of DTT to blood samples aliquots, contributing to the redox thiol status, is not directly involved in the modulation of erythrocyte rheological properties. However, upon acetylcholinesterase modulation by its substrate or inhibitor, changes on the hemorheological parameters are triggered by DTT. Associated pharmacological interest is considerable to address the hemorheology-hemostasis-microcirculation triad disorders.

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Dithiothreitol stimulates the activity of the plasma membrane aminophospholipid translocator

Cited by 11 publications

References 29 publications

Dithiothreitol revisited in red cells: A new head for an old hat

Dithiothreitol revisited in red cells: A new head for an old hat

Vitamin E Inhibits Anti-Fas-Induced Phosphatidylserine Oxidation but Does Not Affect Its Externalization During Apoptosis in Jurkat T Cells and Their Phagocytosis by J774A.1 Macrophages

Modulation of hemorheological parameters by the erythrocyte redox thiol status

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