scholarly journals Size Matters: Molecular Weight Specificity of Hyaluronan Effects in Cell Biology

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Jaime M. Cyphert ◽  
Carol S. Trempus ◽  
Stavros Garantziotis

Hyaluronan signaling properties are unique among other biologically active molecules, that they are apparently not influenced by postsynthetic molecular modification, but by hyaluronan fragment size. This review summarizes the current knowledge about the generation of hyaluronan fragments of different size and size-dependent differences in hyaluronan signaling as well as their downstream biological effects.

2010 ◽  
Vol 1 (1) ◽  
pp. 67-83 ◽  
Author(s):  
Paweł Pasikowski ◽  
Marzena Cydzik ◽  
Alicja Kluczyk ◽  
Piotr Stefanowicz ◽  
Zbigniew Szewczuk

AbstractUbiquitin (Ub) is involved in many key processes of cell biology. Identification of compounds that could interfere in the ubiquitination process is of importance. It could be expected that peptides derived from the Ub-binding regions might be able to interact with Ub receptors themselves and modify an ability of the Ub receptors interactions. This review summarizes current knowledge about known Ub-derived peptides and discusses putative activity of unexplored Ub fragments. Among identified biologically active Ub-derived peptides, its decapeptide fragment of the LEDGRTLSDY sequence was found to exhibit strong immunosuppressive effects on the cellular and humoral immune responses, comparable to that of cyclosporine. Some of the Ub fragments possess strong antibacterial and antifungal potency. In the search for new peptides that could interfere in the interaction of Ub with other proteins, we investigated the pentapeptide Ub sequences present in non-ubiquitin proteins. Based on examination of the Swiss-Prot database, we postulated that sequences of some Ub fragments often exist in other protein molecules. However, some of those motives are represented more frequently than others and could be involved in regulation of cellular processes related to Ub.


Author(s):  
W. Bernard

In comparison to many other fields of ultrastructural research in Cell Biology, the successful exploration of genes and gene activity with the electron microscope in higher organisms is a late conquest. Nucleic acid molecules of Prokaryotes could be successfully visualized already since the early sixties, thanks to the Kleinschmidt spreading technique - and much basic information was obtained concerning the shape, length, molecular weight of viral, mitochondrial and chloroplast nucleic acid. Later, additonal methods revealed denaturation profiles, distinction between single and double strandedness and the use of heteroduplexes-led to gene mapping of relatively simple systems carried out in close connection with other methods of molecular genetics.


1987 ◽  
Vol 58 (04) ◽  
pp. 1064-1067 ◽  
Author(s):  
K Kodama ◽  
B Pasche ◽  
P Olsson ◽  
J Swedenborg ◽  
L Adolfsson ◽  
...  

SummaryThe mode of F Xa inhibition was investigated on a thromboresistant surface with end-point attached partially depoly-merized heparin of an approximate molecular weight of 8000. Affinity chromatography revealed that one fourth of the heparin used in surface coating had high affinity for antithrombin III (AT). The heparin surface adsorbed AT from both human plasma and solutions of purified AT. By increasing the ionic strength in the AT solution the existence of high and low affinity sites could be shown. The uptake of AT was measured and the density of available high and low affinity sites was found to be in the range of 5 HTid 11 pic.omoles/cmf, respectively Thus the estimated density of biologically active high and low ailmity heparm respectively would be 40 and 90 ng/cm2 The heparin coating did not take up or exert F Xa inhibition by itself. With AT adsorbed on both high and low affinity heparin the surface had the capacity to inhibit several consecutive aliquots of F Xa exposed to the surface. When mainly high affinity sites were saturated with AT the inhibition capacity was considerably lower. Tt was demonstrated that the density of AT on both high and low affinity heparin determines the F Xa inhibition capacity whereas the amount of AT on high affinity sites limits the rate of the reaction. This implies that during the inhibition of F Xa there is a continuous surface-diffusion of AT from sites of a lower class to the high affinity sites where the F Xa/AT complex is formed and leaves the surface. The ability of the immobilized heparin to catalyze inhibition of F Xa is likely to be an important component for the thromboresistant properties of a heparin coating with non-compromized AT binding sequences.


Foods ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1556
Author(s):  
Nina Rica Wium Geiker ◽  
Hanne Christine Bertram ◽  
Heddie Mejborn ◽  
Lars O. Dragsted ◽  
Lars Kristensen ◽  
...  

Meat is highly nutritious and contributes with several essential nutrients which are difficult to obtain in the right amounts from other food sources. Industrially processed meat contains preservatives including salts, possibly exerting negative effects on health. During maturation, some processed meat products develop a specific microbiota, forming probiotic metabolites with physiological and biological effects yet unidentified, while the concentration of nutrients also increases. Meat is a source of saturated fatty acids, and current WHO nutrition recommendations advise limiting saturated fat to less than ten percent of total energy consumption. Recent meta-analyses of both observational and randomized controlled trials do not support any effect of saturated fat on cardiovascular disease or diabetes. The current evidence regarding the effect of meat consumption on health is potentially confounded, and there is a need for sufficiently powered high-quality trials assessing the health effects of meat consumption. Future studies should include biomarkers of meat intake, identify metabolic pathways and include detailed study of fermented and other processed meats and their potential of increasing nutrient availability and metabolic effects of compounds.


1994 ◽  
Vol 72 (02) ◽  
pp. 275-280 ◽  
Author(s):  
David Brieger ◽  
Joan Dawes

SummaryIt is widely reported that persistent anti-Xa activity follows administration of low molecular weight heparins. To identify the effectors of this activity we have injected 125I-labelled Enoxaparin sodium into rabbits and subsequently analysed the circulating radiolabelled material and anti-Xa activity by affinity and size exclusion chromatography. Antithrombin III-binding material derived from the injected drug was responsible for all the anti-Xa amidolytic activity. At early times after injection additional anticoagulant activity which was largely attributable to tissue factor pathway inhibitor was measured by the Heptest clotting assay after removal of glycosaminoglycans from plasma samples. Small radiolabelled fragments, including penta/hexasaccharide with affinity for antithrombin III, were detectable in the circulation 1 week later, and sulphated oligosaccharides persisted for 3-4 weeks. Significant quantities of radiolabel remained in the liver and kidney several weeks post-injection; these organs may sequester some of the injected drug and give rise to circulating biologically active material by degradation and secretion of catabolic products into the plasma.


2000 ◽  
Vol 80 (4) ◽  
pp. 1669-1699 ◽  
Author(s):  
Giuseppe Montrucchio ◽  
Giuseppe Alloatti ◽  
Giovanni Camussi

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.


1991 ◽  
Vol 260 (1) ◽  
pp. R126-R133 ◽  
Author(s):  
L. Johannsen ◽  
J. Wecke ◽  
F. Obal ◽  
J. M. Krueger

Muramyl peptides have a variety of biological effects in mammals, including enhancement of the immune response, sleep, and body temperature. Although mammals lack biosynthetic pathways for muramyl peptides, they are found in mammals and are well known as components of bacterial cell walls. This suggests that phagocytic mammalian cells digest bacterial cell walls and produce biologically active muramyl peptides. Staphylococcal cell walls were radioactively labeled during growth of the bacteria. During the digestion of these radiolabeled bacteria, murine bone marrow macrophages produced low-molecular-weight substances that coeluted chromatographically with the radioactive cell wall marker. Further separation of these substances using reversed-phase high-performance liquid chromatography resulted in the isolation of substances with high specific biological activity. Intracerebroventricular injection of rabbits with these substances induced an increase in slow-wave sleep and body temperature and a suppression of rapid-eye-movement sleep. The characteristics of the biological responses and the chromatographic behavior of the active components are consistent with those of muramyl peptides. The ability of macrophages to tailor muramyl peptides from peptidoglycan may provide an amplification step for the immune response. Muramyl peptides released by macrophages may also act as mediators for various facets of the acute phase response elicited by bacterial infections such as fever and sleep.


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Takashi Yokoo ◽  
Kei Matsumoto ◽  
Shinya Yokote

Significant advances have been made in stem cell research over the past decade. A number of nonhematopoietic sources of stem cells (or progenitor cells) have been identified, including endothelial stem cells and neural stem cells. These discoveries have been a major step toward the use of stem cells for potential clinical applications of organ regeneration. Accordingly, kidney regeneration is currently gaining considerable attention to replace kidney dialysis as the ultimate therapeutic strategy for renal failure. However, due to anatomic complications, the kidney is believed to be the hardest organ to regenerate; it is virtually impossible to imagine such a complicated organ being completely rebuilt from pluripotent stem cells by gene or chemical manipulation. Nevertheless, several groups are taking on this big challenge. In this manuscript, current advances in renal stem cell research are reviewed and their usefulness for kidney regeneration discussed. We also reviewed the current knowledge of the emerging field of renal stem cell biology.


Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 235
Author(s):  
Bin Gu ◽  
Maxwell C. Hakun

NUT carcinoma (NC) is a type of aggressive cancer driven by chromosome translocations. Fusion genes between a DNA-binding protein, such as bromodomain and extraterminal domain (BET) proteins, and the testis-specific protein NUTM1 generated by these translocations drive the formation of NC. NC can develop in very young children without significant accumulation of somatic mutations, presenting a relatively clean model to study the genetic etiology of oncogenesis. However, after 20 years of research, a few challenging questions still remain for understanding the mechanism and developing therapeutics for NC. In this short review, we first briefly summarize the current knowledge regarding the molecular mechanism and targeted therapy development of NC. We then raise three challenging questions: (1) What is the cell of origin of NC? (2) How does the germline analogous epigenetic reprogramming process driven by the BET-NUTM1 fusion proteins cause NC? and (3) How will BET-NUTM1 targeted therapies be developed? We propose that with the unprecedented technological advancements in genome editing, animal models, stem cell biology, organoids, and chemical biology, we have unique opportunities to address these challenges.


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