Effect of amino acids on cell proliferation and protein p53 expression in organotypic culture of lymphoid tissue from neonatal rats.

The effect of the larger molecular weight l-amino acids on the development of spleen explants from 1- and 21-day rats in organotypic tissue culture was studied. The amino acids asparagine, lysine, arginine, and glutamic acid inhibited the growth zone of explants of immature tissue from 1-day animals but had an opposite, stimulating, effect on mature spleen tissue of 21-day rats. Immunohistochemical analysis revealed a reciprocal correlation between the expression of the proapoptotic protein, p53, and T-cell proliferation in response to lysine, asparagine, and glutamic acid. Interestingly only arginine reduced the area of p53 expression both in explants of mature and immature spleen tissue. The ability of arginine to reduce p53 expression can be suggested as one of the mechanisms of the tumor growth stimulation.

[The comparative effect of the tetrapeptides and amino acids on the organotypic culture of tissues of young and old rats].

The effect of the synthetic tetrapeptides and amino acids composing them, in concentration 10(-12) M, was investigated in organotypic tissue culture on the cell proliferation and apoptosis development in six tissue explants (ecto-, meso- and entodermal genesis) in 3 and 24 months old rats. The tetrapeptides demonstrated the greater tissue-specificity, as compared to the amino acids. Each tetrapeptide stimulated proliferation in only one corresponded tissue type. The amino acids stimulated proliferation and apoptosis in three-five tissues. It can be suggested, that tissue-specificity in these biologically active substances is depended on the structure complexity. An active amino acids number decreased in old tissues, but tetrapeptides stimulated proliferation both in young and old tissues.

[Functional arginine-containing amino acid sequences in peptides and proteins].

L-arginine is a source of nitrogen oxide and plays a great role in a number of other biochemical processes. Functions and prospects for practical application of five groups of arginine-containing amino acid sequences and synthetic polyarginine sequences are considered. The physiological characteristics of well-known arginine-containing peptides, such as RGD peptides, kyotorphin, and tuftsin, are described in detail. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2008, vol. 34, no. 2; see also http://www.maik.ru

[The comparative analysis of the effect of oligopeptides and amino acids on the development of rat different tissue culture].

The effect the synthetic tetra-, tripeptides and amino acids, composed them, in concentration 10(-12) M was investigated in organotypic tissue culture on the cell proliferation and apoptosis development in six tissue explants (ecto-, meso- and entodermal genesis) in rats at age 3 months old. The tetrapeptide demonstrated the greater tissue-specificity, as compared to the tripeptides and amino acids. Each tetrapeptide stimulated proliferation in only one corresponded tissue type. Less tissue-specificity was observed in the tripeptides, which stimulated proliferation and apoptosis in one (one case)--four tissues. The amino acids stimulated proliferation and apoptosis in three--five tissues. It can be suggested, that tissue-specificity in these biologically active substances is depended on the structure complexity. It is discussed, that the tetrapeptide tissue-specificity is related to the complementar interaction to the DNA site-specific blocks.

[Effect of the arginine and its metabolites on the rat myocardium in organothypic tissue culture in young and old rats].

The arginine and its metabolites were used to investigate the effect on organotypic tissue culture of explants from the spleen, liver, brain cortex and heart of young (3-month old) and aged (18-month old) rats. The arginine effective concentration was 0.5 ng/ml, showed proliferative effect in spleen, liver tissue cultures as compared to the control explants in both groups of rats. No effect of arginine was observed in nervous tissue culture in both groups of rats. The arginine and its metabolites--citrulline, ornitine, urea--stimulate the cell proliferation in miocardium explants in young rats, but not in old. The nitric oxid inhibits the heart explants in young rats.

Effect of amino acids and antibodies against nerve growth factor receptors on the development of organotypic culture of lymphoid tissue.

We studied the effects of 20 L-amino acids on organotypic culture of splenic lymphoid tissue from 3-month-old rats were studied in the presence of apoptosis-inducing monoclonal antibodies against low-affinity receptors for nerve growth factor NGFRp75. The influence of amino acids stimulating cell proliferation in explants (lysine, asparagine, and glutamic acid) did not depend on NGFRp75. Hydrophobic amino acids inhibiting the growth zone in isolated application and abolished the inhibition of explant development in the presence of antibodies against NGFRp75. These amino acids can mediate the proapoptotic effect on lymphoid tissue via low-affinity receptors for nerve growth factor.

[The effect of arginine and its metabolites on tissue culture of rat myocardium].

In was demonstrated using the method of organotypic culture that arginine and its metabolites: cutrulline, ornitine and especially urea, in ultralow doses stimulated the myocardium proliferation in mature rats. Only nitric oxide (NO) possessed the antiproliferative effect. The cytrulline effect was similar to the arginine effect. The metabolism of these amino acids is intimately interrelated so the cytrulline can be used in the clinic practice as an "argininepreserved" preparation. The antiproliferative NO effect can be delayed by thiole-containing preparations: glulathione and unithiole.

[Development of rat spleen organotypic culture under the influence of aminoacids and antibodies against nerve growth factor receptors].

Effect of each of 20 L-aminoacids on spleen organotypic culture of 3 month-old rats was studied in the presence of monoclonal antibodies against low-affinity nerve growth factor (NGF) receptors NGFRp75, which are known to induce apoptosis. It was shown that the action of aminoacids lysine, asparagine and glutamic acid stimulating explant proliferative activity, was independent on NGFRp75. On the contrary, the action of hydrophobic aminoacids, which, if applied separately, inhibited the explant growth, was canceled in the presence of antibodies against NGFRp75. Thus, this group of aminoacids may mediate their proapoptotic effect on lymphoid tissue by means of low-affinity receptors to NGF.

[Effect of amino acids on cell proliferation and apoptosis in organotypic tissue culture of young and old rats].

There was studied in brain cortex, spleen and liver organotypic tissue culture the effect of effective concentrations (0.05 ng/ml) of 20 amino acids on the development of proliferative activity and apoptosis in peripheral fields of explants of rats of various age: 1 month and 18 months old. In the young tissues, the most frequent activity (3 times) was found while using the histidine, asparagine acide, valine, threonine, proline, leucine, tyrosine, methionine, and the less frequent (1 time)--while using lysine, glutamine, cysteine. Almost half number of the amino acids (11) was active in the old tissue cultures, as compared to the young tissues (19). The summary effectiveness of the amino acids was greater in young tissues (42), as compared to the old tissues (11). The data obtained suggest, that the bioregulator peptides should be necessary used to correct the less sensitivity of the tissues to the amino acids in old age.

[The tissue-specific effect of synthetic peptides-biologic regulators in organotypic tissues culture in young and old rats].

The synthetic peptides--cardiogen, bronchogen, prostamax and pancragen were used to investigate their effect on organotypic tissue culture of explants from heart, lungs, prostatic gland and pancreas of young (3-week old) and aged (18-month old) rats. The peptide effective concentration of 0.05 ng/ml showed a stimulating effect in appropriate tissue cultures as compared to the control explants in all groups of rats. So these bioregulatory peptides can be used in clinic practice for the stimulation of reparative processes in the appropriate tissues while ageing.