Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other ...excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides. This review aims to decipher the physiological roles of carnosine, based on its biochemical properties. The latter include pH-buffering, metal-ion chelation, and antioxidant capacity as well as the capacity to protect against formation of advanced glycation and lipoxidation end-products. For these reasons, the therapeutic potential of carnosine supplementation has been tested in numerous diseases in which ischemic or oxidative stress are involved. For several pathologies, such as diabetes and its complications, ocular disease, aging, and neurological disorders, promising preclinical and clinical results have been obtained. Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide. This paper summarizes a century of scientific exploration on the (patho)physiological role of carnosine and related compounds. However, far more experiments in the fields of physiology and related disciplines (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a full understanding of the function and applications of this intriguing molecule.
The modern theory of lipid membrane structure incorporates the concept of lateral stress profile. The latter represents the forces that act on any solute inside the membrane. We used this concept to ...propose two lipid probes that introduce minimal distortions into the lipid bilayer packing: the surface pressure isotherms and volt-potentials of the pure and mixed (probe-containing) lipid monolayers are equal. The probes represent a FRET pair. They are applicable in lipid transfer and vesicle fusion experiments.
Display omitted
•Lateral stress profile is used to predict probes distribution in the bilayer.•FRET pair of probes with very similar structures and distributions is proposed.•The probes introduce minimal distortions into the lipid packing.
Hyperhomocysteinemia is a risk factor for a number of cardiovascular and neurodegenerative processes as well as a complicating factor in normal pregnancy. Toxic effects of homocysteine and the ...product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species. Even a short-term exposure of cells to homocysteic acid at concentrations characteristic of hyperhomocysteinemia induces their apoptotic transformation. The discovery of NMDA receptors both in neuronal tissue and in several other tissues and organs (including immunocompetent cells) makes them a target for toxic action of homocysteine. The neuropeptide carnosine was found to protect the organism from homocysteine toxicity. Treatment of pregnant rats with carnosine under conditions of alimentary hyperhomocysteinemia increases viability and functional activity of their progeny.
In this review, the development of understanding of the biological functions of carnosine is briefly discussed. Carnosine was first described as a component of meat in 1900 by V. S. Gulevitch. ...Changes in the concepts of the role of carnosine in metabolism are followed starting from the early suggestion that it is the end product of protein degradation to the modern ideas based on demonstrating its specific involvement in intracellular signaling regulation in excitable tissue cells. The discovery of the ability of carnosine to regulate expression of early response genes broadens the concept about carnosine as a cellular peptide regulator. The first attempts for application of carnosine in sport and medical practice are described.
Display omitted
•Electronic transmutation was tested in the example of all-Be clusters doped with Li atoms to mimic small Boron cluster.•Electronic transmutation is demonstrated for group 2 to group ...13 elements (Be to B).•LixBex clusters have geometric structures similar to Bx clusters.
We report the results obtained via ab initio studies for electronic transmutation of beryllium to boron. According to the electronic transmutation concept, an element Z, by acquiring an extra electron, begins to exhibit similar chemical bonding and geometric structure properties of compounds composed of neigh- boring elements Z + 1. Comprehensive searches for the most stable structures of LinBen and Bn (n = 3–5) demonstrate that the global minimum isomer of Li3Be3 resembles the chemical bonding and geometric structure of B3. However, for n = 4 and 5, low lying isomers of the Benn--kernels–and not the global minimum–are what resemble their Bn counterparts.
The secreted phospholipases A2 (sPLA2s) play important roles both physiologically and pathologically, with their expression increasing significantly in diseases such as sepsis, inflammation, ...different cancers, glaucoma, obesity, Alzheimer's disease and even COVID-19. The fact has led to a large-scale search for inhibitors of these enzymes. In total, several dozen promising molecules have been proposed, but not a single one has successfully passed clinical trials. The failures in clinical studies motivated in-depth fundamental studies of PLA2s. Here we review alternative ways to control sPLA2 activity, outside its catalytic site. The concept can be realized by preventing sPLA2 from attaching to the membrane surface; by binding to an external protein which blocks sPLA2 hydrolytic activity; by preventing sPLA2 from orienting properly on the membrane surface; and by preventing substrate binding to the enzyme, keeping the catalytic site unaltered. Evidence in the literature is summarized in the review with the aim to serve as a starting point for new types of sPLA2 inhibitors.
This article is devoted to the tool usage as conductive filler with application of electric field for dynamic dimensional finishing combined treatment of hard-to-reach surfaces with high degree of ...curvature. The area of its technological use is shown in relation to aircraft engineering, rocket and space technology component parts and oil and gas industry. The common criterion for method applicability is that such parts have sections with variable curvature and limited tool access to the treatment area. The authors show that in dynamic combined process control of the required technological and operational indicators is possible due to the combination of current-carrying granules kinetic energy and surface anodic dissolution in treatment area. Methods for remote control of dimensional processing with the creation of required reinforced surface layer due to the dynamic mechanical action of solid granules and surface roughness due to anodic dissolution of work surface are presented. The resulting effect is increase in service life and durability in critical assemblies of aerospace equipment and oil and gas apparatus.
This article is devoted to the study of workpieces surface layer state, resulting from dynamic exposure of a two-component electrode with imposition of electric field. The objects considered in the ...work are details with complex profile. Such parts are used in aviation, rocket and space technology and in oil and gas industry. They include impellers and flow part of turbopump bodies, augers, blade wheels, which have areas of variable curvature with limited tool access to treatment area. The authors show that mixture in combined process of two-component processing media from current-carrying granules and conductive liquid medium supplied at high speed to the treatment area, provides the required quality of surface layer due to the combined dynamic exposures on the material being treated. The parameters combination of electric field and kinetic energy of conductive granules allows you to control the magnitude and depth of material hardened layer in treatment area. Experimental studies have shown the increase in resource and durability of critical assemblies for aerospace equipment and oil and gas apparatus.
NMDA receptors play a crucial role in regulating synaptic plasticity and memory. Activation of NMDA receptors changes intracellular concentrations of Na
+
and K
+
, which are subsequently restored by ...Na/K-ATPase. We used immunochemical and biochemical methods to elucidate the potential mechanisms of interaction between these two proteins. We observed that NMDA receptor and Na/K-ATPase interact with each other and this interaction was shown for both isoforms of α subunit (α1 and α3) of Na/K-ATPase expressed in neurons. Using Western blotting, we showed that long-term exposure of the primary culture of cerebellar neurons to nanomolar concentrations of ouabain (a cardiotonic steroid, a specific ligand of Na/K-ATPase) leads to a decrease in the levels of NMDA receptors which is likely mediated by the α3 subunit of Na/K-ATPase. We also observed a decrease in enzymatic activity of the α1 subunit of Na/K-ATPase caused by NMDA receptor activation. This effect is mediated by an increase in intracellular Ca
2+
. Thus, Na/K-ATPase and NMDA receptor can interact functionally by forming a macromolecular complex which can be important for restoring ionic balance after neuronal excitation. Furthermore, this interaction suggests that NMDA receptor function can be regulated by endogenous cardiotonic steroids which recently have been found in cerebrospinal fluid or by pharmacological drugs affecting Na/K-ATPase function.
We describe azophenylindane based molecular motors (aphin-switches) which have two different rotamers of trans-configuration and four different rotamers of cis-configuration. The behaviors of these ...motors were investigated both experimentally and computationally. The conversion of aphin-switch does not yield single isomer but a mixture of these. Although the trans to cis conversion leads to the increase of the system entropy some of the cis-rotamers can directly convert to each other while others should convert via trans-configuration. The motion of aphin-switches resembles the work of a mixing machine with indane group serving as a base and phenol group serving as a beater. The aphin-switches presented herein may provide a basis for promising applications in advanced biological systems or particularly in cases where on demand disordering of molecular packing has value, such as lipid bilayers.
PDF
