Experimental study of the effects of sodium ion concentrations on the function of the myocardium exposed to cardioplegic ischemia.

A new cardioplegic solution based on three natural dipeptides was developed and introduced at the Laboratory of Cardioplegia, A. N. Bakulev Research Center of Cardiovascular Surgery. The electrolyte composition of the solution corresponded to the category of intracellular cardioplegic solutions. The results of 60 experiments on isolated rat hearts were analyzed for choosing the optimal concentration of sodium ions (35, 60, or 80 mmol/liter). The composition of the studied cardioplegic solutions was selected by ion concentrations in the intra- and extracellular fluid. Earlier and most effective recovery of cardiac function with minimum rhythm and conductivity disorders was observed in the group treated with cardioplegic solution with sodium ion concentration of 60 mmol/liter.

Carnosine: new concept for the function of an old molecule.

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.

NMDA receptors in immune competent cells.

This review presents analysis of literature data indicating the presence of NMDA-type glutamate receptors in several types of immune competent cells such as thymocytes, lymphocytes, and neutrophils. The possible role of these receptors in the function of these cells is discussed. The interaction of the receptors with certain ligands circulating in the bloodstream and their role in modulation of immune function is described. It is suggested that homocysteine ​​acts as modulator of these receptors, and its toxicity is largely explained by hyperactivation of the NMDA-type glutamate receptors.

Effect of carnosine and related compounds on proliferation of cultured rat pheochromocytoma PC-12 cells.

The study was undertaken to determine the mechanism of carnosine effect on cell proliferation. We studied the effect of carnosine and its derivatives on cell cycle progression in cultured rat pheochromocytoma cells (PC-12). It was found that 48-h incubation of PC-12 cells with carnosine in concentrations of 10-50 mM led to deceleration of cell proliferation, reduction of G0/G1 peak, and accumulation of S- and G2/M-phase cells. Methylation of the carnosine molecule by 1N-position of the imidazole ring potentiated its effect on cell proliferation. Acetylation of the carnosine molecule by free ß-amino group attenuated its effect.

Effects of carnosine on polyamine levels in red blood cells of patients with hypertonic discirculatory encephalopathy.

The levels of polyamines (putrescine, spermine, spermidine) in erythrocytes from patients with hypertonic discirculatory encephalopathy are reduced (by 37, 45, and 50%, respectively) in comparison with the corresponding parameters in the control group. Addition of carnosine to the treatment protocol for chronic brain ischemia normalized the content of putrescine and spermine. The mechanisms of carnosine influence on polyamine metabolism are discussed: trapping of acrolein, end-product of polyamine oxidation, and compensation of NMDA-receptor excitotoxicity.

Effect of homocysteine on properties of neutrophils activated in vivo.

We have found that neutrophils begin to express NMDA receptors on their membranes after in vivo activation. These receptors are the target for action of homocysteine (HC). After incubation of activated neutrophils with HC, the degranulation process is stimulated and generation of reactive oxygen species is increased. We conclude that expression of NMDA receptors on neutrophil membrane makes neutrophils sensitive to HC. Thus, hyperhomocysteinemia may induce additional stimulation of immune competent cells.

[Portrait of a scientist].

The article is devoted to the analysis of scientific and social activities of academician Sergei Severin whose 110th birthday anniversary comes in 2010. Severin was a well known Russian scientist, the founder of a biochemical school in this country and organizer of the Department of Biochemistry at Lomonosov Moscow State University that he headed for 50 years! Severin belonged to a pleiad of omniscient scholars having numerous followers and disciples. This essay describes his life, creative work and scientific heritage.

[The Na+ pump and intracellular signaling mechanisms].

The main properties of Na+ /K(+)-ATPase as a natural receptor for cardiotonic steroids have been discusses. Primary attention is focused on structural and functional differences between the alpha-subunit isoforms of Na+/K(+)-ATPase in different tissues. General information on the role of the Na pump in signaling cascades in kidney epithelial cells, cardiomyocytes and neurons is presented. The data obtained indicate that, in neurons, several alpha-isoforms of Na+/K(+)-ATPase possessing different sensitivity to ouabain may have different signaling functions.

Biological activity of novel synthetic derivatives of carnosine.

Two novel derivatives of carnosine--(S)-trolox-L-carnosine (STC) and (R)-trolox-L-carnosine (RTC) are characterized in terms of their antioxidant and membrane-stabilizing activities as well as their resistance to serum carnosinase. STC and RTC were synthesized by N-acylation of L-carnosine with (S)- and (R)-trolox, respectively. STC and RTC were found to react more efficiently with 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and protect serum lipoproteins from Fe(2+)-induced oxidation more successfully than carnosine and trolox. At the same time, STC, RTC and trolox suppressed oxidative hemolysis of red blood cells (RBC) less efficiently than carnosine taken in the same concentration. When oxidative stress was induced in suspension of cerebellum granule cells by their incubation with N-methyl-D-aspartate (NMDA), or hydrogen peroxide (H(2)O(2)), both STC and RTC more efficiently decreased accumulation of reactive oxygen species (ROS) than carnosine and trolox. Both STC and RTC were resistant toward hydrolytic degradation by human serum carnosinase. STC and RTC were concluded to demonstrate higher antioxidant capacity and better ability to prevent cerebellar neurons from ROS accumulation than their precursors, carnosine and trolox.

Carnosine as a natural antioxidant and geroprotector: from molecular mechanisms to clinical trials.

Carnosine is a neuroprotective dipeptide consisting of beta-alanine and L-histidine. It demonstrates a number of useful features, including stimulation of brain and muscle microcirculation and a rejuvenating effect on cultured cells. Its activity is based on its antioxidant and antiglycating action that, in addition to heavy metal chelation and pH-buffering ability, makes carnosine an essential factor for preventing neurodegeneration and accumulation of senile features. Recently, carnosine was successfully used to treat patients after brain stroke or patients with Parkinson disease. We conclude that carnosine can be recommended for patients under oxidative stress as a natural remedy having high efficiency and no side effects.

Molecular mechanisms of homocysteine toxicity.

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.

Cardioprotective effect of histidine-containing dipeptides in pharmacological cold cardioplegia.

The cardioprotective effect of cardioplegic solution based on histidine-containing dipeptides was evaluated on isolated rat heart under conditions of hyporthermia and long ischemia. The use of natural dipeptides in cardioplegic solutions promoted an increase in the buffer capacity of myocardial cells and creation of an additional anti-ischemic effect under conditions of long ischemia and hypothermia.

Application of multipotent mesenchymal stromal cells from human adipose tissue for compensation of neurological deficiency induced by 3-nitropropionic Acid in rats.

We evaluated possible therapeutic effect of multipotent mesenchymal stromal cells from human adipose tissue differentiated to neuronal phenotype with retinoic acid on Wistar rats subjected to toxic effect of 3-nitropropionic acid. Transplantation of mesenchymal stromal cells from human adipose tissue considerably decreased neurological symptoms, normalized exploratory activity (open field test) and long-term memory (Morris test), which correlated with normalization of pathomorphological manifestations in the brain. Destructive changes in the caudate nucleus caused by treatment with 3-nitropropionic acid (reduced size of neurons, changes in their shape, and cell edema) tended to decrease under the effect of multipotent mesenchymal stromal cells: the area of neurons increased 2-fold, the cells acquired typical round shape, cell edema decreased.

[Search for chaperon-like anticataract drugs, the antiaggregants of lens crystallins. Communication. 1. Chaperon-like activity of N-acetyl carnosine dipeptide: in vitro study on a model of ultraviolet-induced aggregation of betaL-crystallin].

Aggregation ofcrystallins, the lens proteins, is one of the basic stages of cataract formation. Among the protein aggregation models used to study the molecular mechanisms of the initial stages of lenticular opacity, UV-induced aggregation of betaL-crystallin is most close to the in vivo conditions. The carnosine derivative N-acetyl carnosine has been shown to be effective in inhibiting the UV-induced aggregation of betaL-crystallin. Examination of the accumulation kinetics of carbonyl groups in betaL-crystallin under UV irradiation has indicated that neither carnosine nor N-acetyl carnosine fails to affect this parameter--an indicator of oxidative protein damage. By taking into account also the fact that N-acetyl carnosine is not an antioxidant, it can be believed that the molecular mechanism of action of this compound on UV-induced aggregation of betaL is unassociated with its antioxidative properties. The authors hypothesize that the molecular chaperon-like properties similar to those of alpha-crystallin underlie the mechanism of action of the acetyl derivative carnosine. The prospects for searching anticataract agents of a new chaperon-like class are discussed.

[Carnosine: endogenous physiological corrector of antioxidative system activity].

The results of research of camosine as an antioxidative system corrector in conditions of oxidative stress caused by the action of damaging factors (y-rays, overcooling, hypobaric hypoxia, brain ischemia, neurotoxin impact) are summarized in the present review. The effects of carnosine are characterized not only at the level of the whole organism but also in "in vitro" models with use of a whole series of enzymatic systems. The results of the experiments conducted displayed the ability of carnosine to protect animals from oxidative stress based on the combination of direct antioxidative effects and a modulation of enzymes' activities which participate in controlling of reactive oxygen species level in tissues.

Expression of NMDA receptors in multipotent stromal cells of human adipose tissue under conditions of retinoic acid-induced differentiation.

The system of NMDA glutamate receptors in human adipose tissue multipotent stromal cells and SH-SY5Y human neuroblastoma cells was used as a model for studies of NMDA receptor expression during neurodifferntiation. Glutamate NMDA receptors were detected in multipotent stromal cells of human adipose tissue. The expression of NRI subunits of NMDA receptors increased significantly after 6-day incubation of multipotent stromal cells of human adipose tissue with 10 microM retinoic acid. Only NR1 subunits of NMDA receptors were expressed in SH-SY5Y neuroblastoma cells. Incubation with retinoic acid did not promote the appearance of mRNA of other subunits (NR2A-D, NR3). The results indicate that expression of NMDA receptors can serve as an indicator of neuronal differentiation of cells and as a marker of the efficiency of neuronal differentiation protocol.