An intestinal paracellular pathway biased toward positively-charged macromolecules

The formation of glomerular ultrafiltrate is dependent on the interplay of glomerular pressures and flows as well as the intrinsic permselectivity properties of the glomerular capillary wall. These intrinsic permeability properties serve to exclude macromolecules from the urinary space, based on size as well as net molecular charge discrimination. Neutral dextrans with molecular radii less than 20 A cross the glomerular wall without measurable restriction, whereas dextrans with radii greater than 42 A are almost completely barred. For any given size, negatively charged macromolecules are restricted to a greater extent than neutral molecules. Additionally, positively charged molecules are enhanced in their ability to cross the glomerular wall compared to similarly sized neutral polymers. The concept of a charge barrier, due to fixed negative charges within the glomerular wall, is also supported by morphological studies. Glomerular injury, leading to proteinuria, has been associated with loss of the charge-selective properties of these capillaries. Loss of glomerular fixed negative charges may also result in the foot process fusion and mesangial cell dysfunction often observed in proteinuric states.

Download Full-text

Hyaluronic Acid Inhibits Polycation Induced Cellular Responses

Mediators of Inflammation ◽

10.1155/s0962935194000396 ◽

1994 ◽

Vol 3 (4) ◽

pp. 287-289 ◽

Cited By ~ 1

Author(s):

A. lalenti ◽

A. lanaro ◽

G. Brignola ◽

P. Marotta ◽

M. Di Rosa

Keyword(s):

Hyaluronic Acid ◽

Rabbit Aorta ◽

Target Cells ◽

Anionic Sites ◽

Nitric Oxide Formation ◽

Paw Oedema ◽

Charged Macromolecules ◽

Rat Paw ◽

Rat Paw Oedema ◽

Positively Charged

Positively charged macromolecules cause a variety of pathological events through their electrostatic interaction with anionic sites present on the membrane of target cells. In the present study we have investigated the effect of hyaluronic acid, a negatively charged molecule, on rat paw oedema induced by poly-L-lysine as well as on histamine release from rat mast cells and nitric oxide formation from rabbit aorta, both induced by this polycation. The results indicate that hyaluronic acid is able to suppress these poly-L-lysine induced effects with a mechanism which possibly depends on its negative charges which may balance the effects of positively charged polycations.

Download Full-text

Cationized serum albumin enhances basal and stimulated adenylate cyclase activity in canine renal membranes

Acta Endocrinologica ◽

10.1530/acta.0.1160267 ◽

1987 ◽

Vol 116 (2) ◽

pp. 267-274

Author(s):

N. Nijs-De Wolf ◽

J. Corvilain ◽

P. J. Bergmann

Keyword(s):

Adenylate Cyclase ◽

Serum Albumin ◽

Specific Binding ◽

Human Albumin ◽

Biologically Active ◽

Cyclase Activity ◽

Adenylate Cyclase Activity ◽

Increased Sensitivity ◽

Charged Macromolecules ◽

Positively Charged

Abstract. We examined the effects of cationized serum albumin on the canine renal membrane adenylate cyclase in the basal state and when stimulated with guanylyl-imidodiphosphate, PTH or NaF. Human albumin was cationized to an isoelectric point greater than 9.5 by the addition of hexamethylene diamine. Cationized albumin increased basal and stimulated cAMP production by the membranes and increased the sensitivity of the system to low doses of PTH (0.25 pmol/l), being usually inactive in buffer alone or in human serum albumin. These observations are comparable to those previously reported on thyroid membranes and cells from adrenal tumours and confirm that positively charged macromolecules can increase adenylate cyclase activity. A decrease in non-specific binding of PTH is only partly responsible for the increased sensitivity to the hormone. Though this increase in sensitivity is small, it could nevertheless be useful in the detection of biologically active PTH after extraction from the serum.

Download Full-text

Spontaneous Loading of Positively Charged Macromolecules into Alginate-Templated Polyelectrolyte Multilayer Microcapsules

Biomacromolecules ◽

10.1021/bm0501656 ◽

2005 ◽

Vol 6 (4) ◽

pp. 2221-2228 ◽

Cited By ~ 83

Author(s):

Huiguang Zhu ◽

Rohit Srivastava ◽

Michael J. McShane

Keyword(s):

Polyelectrolyte Multilayer ◽

Charged Macromolecules ◽

Positively Charged

Download Full-text

Protamine-DNA interaction

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100081863 ◽

1978 ◽

Vol 36 (2) ◽

pp. 200-201

Author(s):

D.P. Bazett-Jones ◽

F.P. Ottensmeyer

Keyword(s):

Small Volume ◽

Double Helix ◽

Dna Interaction ◽

Dark Field ◽

Sperm Head ◽

Nuclear Proteins ◽

Field Electron Microscopy ◽

Dark Field Electron ◽

Dna Double Helix ◽

Positively Charged

Dark field electron microscopy has been used for the study of the structure of individual macromolecules with a resolution to at least the 5Å level. The use of this technique has been extended to the investigation of structure of interacting molecules, particularly the interaction between DNA and fish protamine, a class of basic nuclear proteins of molecular weight 4,000 daltons.Protamine, which is synthesized during spermatogenesis, binds to chromatin, displaces the somatic histones and wraps up the DNA to fit into the small volume of the sperm head. It has been proposed that protamine, existing as an extended polypeptide, winds around the minor groove of the DNA double helix, with protamine's positively-charged arginines lining up with the negatively-charged phosphates of DNA. However, viewing protamine as an extended protein is inconsistent with the results obtained in our laboratory.

Download Full-text

Structure and Interaction of Protamine by Dark Field Electron Microscopy

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100090786 ◽

1976 ◽

Vol 34 ◽

pp. 160-161

Author(s):

D.P. Bazett-Jones ◽

F.P. Ottensmeyer

Keyword(s):

Electron Microscopy ◽

Dark Field ◽

Amino Acid Sequences ◽

Dimensional Structure ◽

3 Dimensional ◽

Field Electron ◽

Proposed Model ◽

Field Electron Microscopy ◽

Dark Field Electron ◽

Positively Charged

It has been shown for some time that it is possible to obtain images of small unstained proteins, with a resolution of approximately 5Å using dark field electron microscopy (1,2). Applying this technique, we have observed a uniformity in size and shape of the 2-dimensional images of pure specimens of fish protamines (salmon, herring (clupeine, Y-l) and rainbow trout (Salmo irideus)). On the basis of these images, a model for the 3-dimensional structure of the fish protamines has been proposed (2).The known amino acid sequences of fish protamines show stretches of positively charged arginines, separated by regions of neutral amino acids (3). The proposed model for protamine structure (2) consists of an irregular, right-handed helix with the segments of adjacent arginines forming the loops of the coil.

Download Full-text

Enhanced type I photoreaction of indocyanine green via electrostatic-force-driven aggregation

Nanoscale ◽

10.1039/d0nr01208d ◽

2020 ◽

Vol 12 (17) ◽

pp. 9517-9523 ◽

Cited By ~ 3

Author(s):

Huizhen Fan ◽

Yu Fan ◽

Wenna Du ◽

Rui Cai ◽

Xinshuang Gao ◽

...

Keyword(s):

Mesoporous Silica ◽

Indocyanine Green ◽

Electrostatic Force ◽

Type I ◽

Positively Charged

ICG forms aggregates in positively charged mesoporous silica, which show an enhanced type I photoreaction pathway.

Download Full-text

Influence of nascent polypeptide positive charges on translation dynamics

Biochemical Journal ◽

10.1042/bcj20200303 ◽

2020 ◽

Vol 477 (15) ◽

pp. 2921-2934

Author(s):

Rodrigo D. Requião ◽

Géssica C. Barros ◽

Tatiana Domitrovic ◽

Fernando L. Palhano

Keyword(s):

Mrna Decay ◽

Translation Termination ◽

Published Data ◽

Translation Efficiency ◽

Amino Acid Residues ◽

High Concentration ◽

Strong Argument ◽

Translation Arrest ◽

Exit Tunnel ◽

Positively Charged

Protein segments with a high concentration of positively charged amino acid residues are often used in reporter constructs designed to activate ribosomal mRNA/protein decay pathways, such as those involving nonstop mRNA decay (NSD), no-go mRNA decay (NGD) and the ribosome quality control (RQC) complex. It has been proposed that the electrostatic interaction of the positively charged nascent peptide with the negatively charged ribosomal exit tunnel leads to translation arrest. When stalled long enough, the translation process is terminated with the degradation of the transcript and an incomplete protein. Although early experiments made a strong argument for this mechanism, other features associated with positively charged reporters, such as codon bias and mRNA and protein structure, have emerged as potent inducers of ribosome stalling. We carefully reviewed the published data on the protein and mRNA expression of artificial constructs with diverse compositions as assessed in different organisms. We concluded that, although polybasic sequences generally lead to lower translation efficiency, it appears that an aggravating factor, such as a nonoptimal codon composition, is necessary to cause translation termination events.

Download Full-text

Characteristics of the Interaction between Thrombin Exosite1 and the Sequence 269-297 of Platelet Glycoprotein Ibα

Thrombosis and Haemostasis ◽

10.1055/s-0037-1615193 ◽

1998 ◽

Vol 80 (08) ◽

pp. 310-315 ◽

Cited By ~ 8

Author(s):

Marie-Christine Bouton ◽

Christophe Thurieau ◽

Marie-Claude Guillin ◽

Martine Jandrot-Perrus

Keyword(s):

Platelet Activation ◽

Electrostatic Interactions ◽

Platelet Glycoprotein ◽

Thrombin Receptor ◽

Central Position ◽

Amidolytic Activity ◽

N Terminus ◽

Hydrolysis Of ◽

Chemical Cross Linking ◽

Positively Charged

SummaryThe interaction between GPIb and thrombin promotes platelet activation elicited via the hydrolysis of the thrombin receptor and involves structures located on the segment 238-290 within the N-terminal domain of GPIbα and the positively charged exosite 1 on thrombin. We have investigated the ability of peptides derived from the 269-287 sequence of GPIbα to interact with thrombin. Three peptides were synthesized, including Ibα 269-287 and two scrambled peptides R1 and R2 which are comparable to Ibα 269-287 with regards to their content and distribution of anionic residues. However, R2 differs from both Ibα 269-287 and R1 by the shifting of one proline from a central position to the N-terminus. By chemical cross-linking, we observed the formation of a complex between 125I-Ibα 269-287 and α-thrombin that was inhibited by hirudin, the C-terminal peptide of hirudin, sodium pyrophosphate but not by heparin. The complex did not form when γ-thrombin was substituted for α-thrombin. Ibα 269-287 produced only slight changes in thrombin amidolytic activity and inhibited thrombin binding to fibrin. R1 and R2 also formed complexes with α-thrombin, modified slightly its catalytic activity and inhibited its binding to fibrin. Peptides Ibα 269-287 and R1 inhibited platelet aggregation and secretion induced by low thrombin concentrations whereas R2 was without effect. Our results indicate that Ibα 269-287 interacts with thrombin exosite 1 via mainly electrostatic interactions, which explains why the scrambled peptides also interact with exosite 1. Nevertheless, the lack of effect of R2 on thrombin-induced platelet activation suggests that proline 280 is important for thrombin interaction with GPIb.

Download Full-text