scholarly journals The plasma membrane of Leishmania donovani promastigotes is the main target for CA(1–8)M(1–18), a synthetic cecropin A–melittin hybrid peptide

1998 ◽  
Vol 330 (1) ◽  
pp. 453-460 ◽  
Author(s):  
Pilar DÍAZ-ACHIRICA ◽  
Josep UBACH ◽  
Almudena GUINEA ◽  
David ANDREU ◽  
Luis RIVAS
Keyword(s):  
Plasma Membrane ◽  
Leishmania Donovani ◽  
Hybrid Peptide ◽  
Fast Kinetics ◽  
Micromolar Concentration ◽  
Cecropin A ◽  
Main Target ◽  
Membrane Effects ◽  
Leishmania Promastigotes ◽  
Kinetics Of

Reports on the lethal activity of animal antibiotic peptides have largely focused on bacterial rather than eukaryotic targets. In these, involvement of internal organelles as well as mechanisms different from those of prokaryotic cells have been described. CA(1-8)M(1-18) is a synthetic cecropin A-melittin hybrid peptide with leishmanicidal activity. Using Leishmania donovani promastigotes as a model system we have studied the mechanism of action of CA(1-8)M(1-18), its two parental peptides and two analogues. At micromolar concentration CA(1-8)M(1-18) induces a fast permeability to H+/OH-, collapse of membrane potential and morphological damage to the plasma membrane. Effects on other organelles are related to the loss of internal homeostasis of the parasite rather than to a direct effect of the peptide. Despite the fast kinetics of the process, the parasite is able to deactivate in part the effect of the peptide, as shown by the higher activity of the d-enantiomer of CA(1-8)M(1-18). Electrostatic interaction between the peptide and the promastigote membrane, the first event in the lethal sequence, is inhibited by polyanionic polysaccharides, including its own lipophosphoglycan. Thus, in common with bacteria, the action of CA(1-8)M(1-18) on Leishmania promastigotes has the same plasma membrane as target, but is unique in that different peptides show patterns of activity that resemble those observed on eukaryotic cells.

scholarly journals N-Terminal Fatty Acid Substitution Increases the Leishmanicidal Activity of CA(1-7)M(2-9), a Cecropin-Melittin Hybrid Peptide

2001 ◽  
Vol 45 (9) ◽  
pp. 2441-2449 ◽  
Author(s):  
Cristina Chicharro ◽  
Cesare Granata ◽  
Rosario Lozano ◽  
David Andreu ◽  
Luis Rivas
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Nucleic Acid Binding ◽  
Hybrid Peptide ◽  
Fast Kinetics ◽  
Leishmanicidal Activity ◽  
Fatty Acid Chain ◽  
Sytox Green ◽  
Cecropin A ◽  
Plasma Membrane Permeabilization

ABSTRACT In order to improve the leishmanicidal activity of the synthetic cecropin A-melittin hybrid peptide CA(1-7)M(2-9) (KWKLFKKIGAVLKVL-NH2), a systematic study of its acylation with saturated linear fatty acids was carried out. Acylation of the Nɛ-7 lysine residue led to a drastic decrease in leishmanicidal activity, whereas acylation at lysine 1, in either the α or the ɛ NH2 group, increased up to 3 times the activity of the peptide against promastigotes and increased up to 15 times the activity of the peptide against amastigotes. Leishmanicidal activity increased with the length of the fatty acid chain, reaching a maximum for the lauroyl analogue (12 carbons). According to the fast kinetics, dissipation of membrane potential, and parasite membrane permeability to the nucleic acid binding probe SYTOX green, the lethal mechanism was directly related to plasma membrane permeabilization.

Single atom catalysts supported on N-doped graphene toward fast kinetic Li−S batteries: a theoretical study

2021 ◽  
Author(s):  
Xu Han ◽  
Zeyun Zhang ◽  
Xuefei Xu
Keyword(s):  
Theoretical Study ◽  
Single Atom ◽  
Discharge Process ◽  
Fast Kinetics ◽  
Shuttle Effect ◽  
Sufficient Stability ◽  
Doped Graphene ◽  
Fast Kinetic ◽  
Kinetics Of ◽  
Charge Discharge

To suppress the shuttle effect of lithium polysulfides and promote fast kinetics of charge−discharge process in Li−S batteries, it is essential to search promising catalysts with sufficient stability and high...

scholarly journals Allosteric modulation of Leishmania donovani plasma membrane Ca(2+)-ATPase by endogenous calmodulin.

1992 ◽  
Vol 267 (26) ◽  
pp. 18440-18446
Author(s):  
S Mazumder ◽  
T Mukherjee ◽  
J Ghosh ◽  
M Ray ◽  
A Bhaduri
Keyword(s):  
Plasma Membrane ◽  
Leishmania Donovani ◽  
Allosteric Modulation

scholarly journals The poly(ADP-ribose)-dependent chromatin remodeler Alc1 induces local chromatin relaxation upon DNA damage

2016 ◽  
Vol 27 (24) ◽  
pp. 3791-3799 ◽  
Author(s):  
Hafida Sellou ◽  
Théo Lebeaupin ◽  
Catherine Chapuis ◽  
Rebecca Smith ◽  
Anna Hegele ◽  
...  
Keyword(s):  
Dna Damage ◽  
Structural Changes ◽  
Cellular Responses ◽  
Dna Lesions ◽  
Fast Kinetics ◽  
Important Player ◽  
Chromatin Relaxation ◽  
Kinetics Of ◽  
Laser Microirradiation

Chromatin relaxation is one of the earliest cellular responses to DNA damage. However, what determines these structural changes, including their ATP requirement, is not well understood. Using live-cell imaging and laser microirradiation to induce DNA lesions, we show that the local chromatin relaxation at DNA damage sites is regulated by PARP1 enzymatic activity. We also report that H1 is mobilized at DNA damage sites, but, since this mobilization is largely independent of poly(ADP-ribosyl)ation, it cannot solely explain the chromatin relaxation. Finally, we demonstrate the involvement of Alc1, a poly(ADP-ribose)- and ATP-dependent remodeler, in the chromatin-relaxation process. Deletion of Alc1 impairs chromatin relaxation after DNA damage, while its overexpression strongly enhances relaxation. Altogether our results identify Alc1 as an important player in the fast kinetics of the NAD+- and ATP-dependent chromatin relaxation upon DNA damage in vivo.

scholarly journals Insulin Stimulates Membrane Fusion and GLUT4 Accumulation in Clathrin Coats on Adipocyte Plasma Membranes

2007 ◽  
Vol 27 (9) ◽  
pp. 3456-3469 ◽  
Author(s):  
Shaohui Huang ◽  
Larry M. Lifshitz ◽  
Christine Jones ◽  
Karl D. Bellve ◽  
Clive Standley ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Fusion ◽  
Insulin Signaling ◽  
Plasma Membranes ◽  
Glucose Transporter ◽  
Fluorescent Protein ◽  
Fluorescent Proteins ◽  
Tirf Microscopy ◽  
Adipocyte Plasma Membranes ◽  
Kinetics Of

ABSTRACT Total internal reflection fluorescence (TIRF) microscopy reveals highly mobile structures containing enhanced green fluorescent protein-tagged glucose transporter 4 (GLUT4) within a zone about 100 nm beneath the plasma membrane of 3T3-L1 adipocytes. We developed a computer program (Fusion Assistant) that enables direct analysis of the docking/fusion kinetics of hundreds of exocytic fusion events. Insulin stimulation increases the fusion frequency of exocytic GLUT4 vesicles by ∼4-fold, increasing GLUT4 content in the plasma membrane. Remarkably, insulin signaling modulates the kinetics of the fusion process, decreasing the vesicle tethering/docking duration prior to membrane fusion. In contrast, the kinetics of GLUT4 molecules spreading out in the plasma membrane from exocytic fusion sites is unchanged by insulin. As GLUT4 accumulates in the plasma membrane, it is also immobilized in punctate structures on the cell surface. A previous report suggested these structures are exocytic fusion sites (Lizunov et al., J. Cell Biol. 169:481-489, 2005). However, two-color TIRF microscopy using fluorescent proteins fused to clathrin light chain or GLUT4 reveals these structures are clathrin-coated patches. Taken together, these data show that insulin signaling accelerates the transition from docking of GLUT4-containing vesicles to their fusion with the plasma membrane and promotes GLUT4 accumulation in clathrin-based endocytic structures on the plasma membrane.

The effects of acetylcholine and atropine on the 22Na+ permeability of intestinal smooth muscle vesicles

1978 ◽  
Vol 56 (6) ◽  
pp. 921-925
Author(s):  
L. Spero
Keyword(s):  
Smooth Muscle ◽  
Plasma Membrane ◽  
Membrane Vesicles ◽  
Intestinal Smooth Muscle ◽  
Erythrocyte Ghosts ◽  
Muscarinic Agonists ◽  
Plasma Membrane Vesicles ◽  
Muscle Plasma Membrane ◽  
Whole Muscle ◽  
Kinetics Of

A technique is described which has enabled us to measure changes in 22Na+ efflux from smooth muscle plasma membrane vesicles. The resting 22Na+ efflux from these sealed vesicles showed a concentration-dependent increase in response to acetylcholine and other muscarinic agonists, in similar concentrations to those which increased 42K+ efflux in whole muscle. The kinetics of this efflux were complex and could not be described by less than three exponential processes. The response to agonists has, therefore, been characterized by measurement of the half-life of 22Na+ efflux (t1/2). The acetylcholine effect was inhibited by atropine, but unlike the situation in the whole muscle, this inhibition was noncompetitive. Tubocuraine (a nicotinic antagonist) had no effect on this acetylcholine response. Atropine has no effect by itself on the resting 22Na+ efflux, neither did tetrodotoxin or ouabain. 22Na+ efflux from erythrocyte ghosts and liposomes, prepared from lipid extracts of the smooth muscle plasma membrane, was not modified by acetylcholine or atropine.

scholarly journals Psychomotor stimulant effects of α-pyrrolidinovalerophenone (αPVP) enantiomers correlate with drug binding kinetics at the dopamine transporter

2021 ◽  
Author(s):  
Marco Niello ◽  
Spyridon Sideromenos ◽  
Ralph Gradisch ◽  
Ronan O'Shea ◽  
Jakob Schwazer ◽  
...  
Keyword(s):  
Dopamine Transporter ◽  
In Silico ◽  
Drug Binding ◽  
Binding Kinetics ◽  
Irreversible Binding ◽  
Fast Kinetics ◽  
Slow Dissociation ◽  
Kinetics Of

Abstract α-Pyrrolidinovalerophenone (αPVP) is a psychostimulant and drug of abuse associated with severe intoxications in humans. αPVP exerts long-lasting psychostimulant effects, when compared to the classical dopamine transporter (DAT) inhibitor cocaine. Here, we compared the two enantiomeric forms of αPVP, the R- and the S-αPVP, with cocaine using a combination of in silico, in vitro and in vivo approaches. We found that αPVP enantiomers substantially differ from cocaine in their binding kinetics. The two enantiomers differ from each other in their association rates. However, they show similar slow dissociation rates leading to pseudo-irreversible binding kinetics at DAT. The pseudo-irreversible binding kinetics of αPVP is responsible for the observed non-competitive pharmacology and it correlates with persistent psychostimulant effects in mice. Thus, the slow binding kinetics of αPVP enantiomers profoundly differ from the fast kinetics of cocaine both in vitro and in vivo, suggesting drug-binding kinetics as a potential driver of psychostimulant effects in vivo.

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