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Biomedical subjects

L S Iaguzhinskiĭ

Publications and source records attributed to L S Iaguzhinskiĭ.

At least 19 recordsLinked to original sources

[Dynamics of mitochondrial ultrastructure in small pieces of cardiac tissue under long-term anoxic incubation].

Anoxic incubation of isolated small pieces of cardiac tissue for 72 h caused emergence of an unusual population of mitochondria, referred to as "mitochondrion inside mitochondrion". We studied dynamics of the origin of this event. In the most part of a mitochondrial population after a 6 h anoxic incubation of myocardial tissue, a local increase in some region of the intermembrane space was observed. Some regions of matrix with adjoined inner membrane move into these regions of intermembrane space, to be constricted eventually. After 12 h of incubation densely neighbouring layers of membrane are observed in these structures. By 24 h of incubation, inside new-formed structures well-distinguished concentric layers of membrane appear. Between these layers some electron-dense material ultrastructurally identical to mitochondrial matrix is seen. By 72 h of anoxic incubation, in cardiomyocytes of the experimental tissue structures with well-marked morphological features of mitochondria appear, which we called "mitochondrion inside mitochondrion". Results of our study are discussed in terms of a conception of changes that occur in the structure of mitochondrial reticulum during apoptosis.

Animals↗

[Ultrastructure of mitochondria apparatus of cardiomyocytes in apoptosis induced by long-term anoxia in rats].

Apoptosis in cardiomyocytes was induced by incubation of pieces of cardiac tissues under condition of anoxia. Electronmicroscopic investigation detected previously unknown changes in mitochondrial ultrastructure. The mitochondrial population was characterized by morphological heterogeneity. In addition to a mitochondrial population characterized with irrigated cleared matrix, anoxia induced the appearance of an atypical and previously unknown population of small electron-dense cardiomyocyte mitochondria. They were characterized by unusual localization inside electron-light mitochondria ("mitochondria inside mitochondria"). The most part of mitochondria with the irrigated matrix are commonly characterized by unusual types of rearrangements of the inner mitochondrial membrane. Under anoxic conditions, the inner mitochondrial membrane formed electron-dense ordered structures. This is a spongy structure with cells of equal size. Results of our study are discussed in terms of conception of changes in mitochondrial reticulum ultrastructure during apoptosis.

Animals↗

[The effect of inhibitors of the Q-cycle on cyano-resistant oxidation of malate by rat liver mitochondria in the presence of menadione].

Based on the inhibitor analysis data, it has been assumed that the Q-cycle plays a role in the cyano-resistant malate oxidation induced by menadione (90 microM) in rat liver mitochondria. The extent of involvement of Q-cycle transmitters in the cyano-resistant respiration of mitochondria is determined by the mode of the electron supply into the Q-cycle. In the presence of dicumarol, i.e., under conditions when CoQ and menadione are reduced by NADH-quinone reductase, the bulk of the electrons pass through the o-center of the Q-cycle. Myxothiazole inhibits the respiration by 70-80%, while antimycin--by only 20-30%. In the presence of myxothiazole and antimycin menadione oxidizes cytochrome b. In the presence of rotenone, when menadione is reduced by DT-diaphorase, the rate of cyano-resistant respiration decreases approximately twofold; its sensitivity towards myxothiazole and antimycin drops down to 40%. In the absence of rotenone and dicumarol the Q-cycle does not participate in the cyano-resistant respiration which under these conditions is insensitive either to myxothiazole or to antimycin. It is concluded that the mechanism of cyano-resistant respiration changes with an alteration in the rates of quinones K3 and CoQ reduction. The mechanism of cyano-resistant respiration is also controlled by the medium tonicity. A reduction in the medium tonicity decrease the participation of the Q-cycle and, correspondingly, the sensitivity of the cyano-resistant respiration towards myxothiazole and antimycin.

Animals↗

[Mitochondrial proteolipids].

A convenient procedure is proposed for extracting mitochondrial proteolipids using a single phase mixture chloroform-methanol-water (1:2:0.8 v/v) with subsequent separation of the phases. The proteolipids were concentrated at the interface between the phases and thus purified from the bulk of the phospholipids. It was found that the mitochondrial proteolipids represent stable complexes of phospholipids with some low molecular weight proteins (M(r) = 7-18 kDa). The latter are destroyed at acid pH values. The phospholipid/protein ratio was found to be equal to 6 (assuming the molecular masses of the proteins and phospholipids to be equal to 10 and 0.8 kDa, respectively). The phospholipid composition of the tightly bound proteolipids thus obtained did not differ from that of the mitochondrial phospholipids. Using 31P-NMR, nonbilayer structures were found to arise from proteolipid reconstitution into multibilayer liposomes.

Animals↗

[The effect of the composition of phospholipid bilayer membranes on the steady state kinetic transfer of protons].

When the hydrogen ion flux was induced by nigericin across the planar bilayer lipid membrane (BLM) with the bulk pHs being equal at the opposite sides of the BLM, the formation of the boundary potential difference (delta phi b) on the BLM was observed using the method of the inner membrane field compensation. The increase in the buffer (citrate, phosphate, MES) concentration caused a decrease in the delta phi b. The latter is generated in the presence of phosphatidylserine in membrane-forming solutions only. It was assumed that the steady state difference of the surface hydrogen ion concentration is created under conditions of equal pHs near the BLM surface. In another experimental series the monensin-mediated formation of the surface protein concentration difference gave rise to the formation of a potassium ion gradient induced by nigericin. Thus, a possibility of performing work due to the surface proton concentration gradient was demonstrated. The relevance of these findings to the processes of energy transduction during membrane phosphorylation in mitochondria and chloroplasts is discussed.

Biological Transport↗

[Five classes of anticarcinogens--phorbol ester antagonists].

Literary data concerning structure-activity relationships in compounds exhibiting an antipromoter activity in skin tests of full tumour promotion by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or its analogs have been reviewed. Five classes of antipromoters differing in their action on the first and second stages of tumour promotion have been identified, namely: i) 2nd stage promoters/1st stage inhibitors; ii) 1st stage promoters/2nd stage inhibitors; iii) 2nd stage inhibitors; iiii) 1st stage inhibitors; iiiii) 1st and 2nd stage inhibitors. The results on structure-activity of antipromoters were compared with the results of previous studies on phorbol tumour promoters. These data made it possible to determine the reciprocal localization of binding sites for various classes of antipromoters and individual functionally important phorbol fragments on protein kinase C. A new detailed variant of the model of two-center binding of full phorbol tumour promoters on protein kinase C is proposed.

Animals↗

[Interaction of menadione and duroquinone with Q-cycle during DT-diaphorase function].

The interaction of quinones (menadione and duroquinone) with DT-diaphorase and mitochondrial electron transport chain translocators at low (120 mosM) and high (400 mosM) values of the medium tonicity in the quinone concentration range of 6-90 microM was studied. It was shown that with a rise in menadione (K3) concentration the number of electron transport carriers interacting with it increase. At K3 concentration of 6 microM the latter is reduced by DT-diaphorase and fully oxidized via the Q-cycle. At K3 concentration of 15 microM the latter is also reduced by DT-diaphorase via the Q-cycle, but in this case the oxidation is incomplete (about 30% K3H2 is oxidized by the terminal part of the respiratory chain). At 90 microM K3 50% of quinone is reduced by DT-diaphorase and 50% by the respiratory chain NADH dehydrogenase complex enzymes; about 30% of K3H2 is oxidized via the Q-cycle, about 20%--by the terminal part of the respiratory chain and about 50%--by O2 without cytochrome oxidase. Unlike menadione, duroquinone (6-90 microM) is reduced only by DT-diaphorase and is oxidized in all cases by cytochrome oxidase. It was shown that the increase in the mitochondrial matrix volume in low tonicity media decreases the rate of the DT-diaphorase shunt operation.

Animals↗

[Complexes of phorbol tumor promoters with protein kinase C].

Based on the literature data, a systematic comparison of relationships between the structures of incomplete and complete phorbol tumor promoters, diacylglycerols and their activities in various biological test-systems was carried out. The specific features of the phorbol esters-protein kinase C complexes responsible for the induction of the first and second stages of the tumor promotion in mouse skin, were established. The type of diacylglycerol binding to protein kinase C which confers to the latter noncarcinogenic properties, was specified.

Animals↗

[Changes in the level of tightly-bound mitochondrial phospholipids induced by exogenous factors].

The effects of some parameters of the incubation medium (tonicity, H+ and Pi concentration) on the phospholipid content in rat mitochondrial extracts prepared by normal extraction and by extraction with strongly acidified solvent mixtures, were studied. It was found that after normal extraction with a chloroform-methanol mixture, 8% to 25% of mitochondrial phospholipids can be additionally extracted by acidified solvent mixtures. The concentration of weakly extractable lipids depends on the tonicity and ionic composition of the incubation medium. It was suggested that there exist in mitochondria two lipid pools, a loosely and a tightly-bound ones; the equilibrium between these pools is effectively regulated by medium tonicity and other external factors.

Animals↗

[Two qualitatively different structuro-functional states of mitochondria].

Low (120 mosM) tonicity of incubation media of mitochondria was found to be associated with anomalous phase transition at 19--26 degrees C. A rise in temperature caused a decrease in the pyrene excitation in border lipids of the mitochondrial membrane. Within this temperature range the quenching of intrinsic protein fluorescence by pyrene was sharply decreased. It may be inferred from these data that at 100mosM tonicity and temperatures below 19 degrees C, mitochondrial membrane proteins are in an aggregated state. At temperatures above phase transition protein deaggregation takes place. It was shown that a decrease in tonicity from 300 to 120 mosM at 15 degrees C or a rise in temperature from 15 degrees to 37 degrees C at 300 mosM tonicity increased the phosphorylation of the 52 kDa mitochondrial protein. It was assumed that swelling of mitochondria in hypotonic media simulates one of the steps of the hormone-induced signal transfer in mitochondria in vivo.

Animals↗

[A study of the mechanism of cyanide resistant oxidation of succinate from rat liver mitochondria in the presence of menadione].

Two operation regimes of the electron transport system were found in rat liver mitochondria during the cyanide-resistant succinate oxidation catalyzed by menadione. Under isotonic conditions, the mitochondria were found to contain two electron transport components, one of which was sensitive to mucidin, whereas the other one was inhibited by antimycin A. Both electron transport components were inhibited by thenoyltrifluoroacetone (TTFA). In hypotonic media, the polyenzymatic respiratory complex of mitochondria underwent transformations. In this case the electron transport during the cyanide-resistant succinate oxidation was insensitive to mucidin and antimycin A and was suppressed only by TTFA. Some experimental evidence in favour of pathways of electron transfer under different regimes of mitochondrial function was obtained. It was supposed that in isotonic incubation media the cyanide-resistant respiration is mainly due to menadione reduction in two points of the Q-cycle, i.e., in the region of the "i" center and in the "o" center. Under hypotonic conditions, the main electron flux to menadione occurs only via the Q-cycle "i" center. The observed relatively slow reduction of cytochromes b and ci+c plays an insignificant role in the cyanide-resistant respiration. It was shown that the ability of menadione to stimulate the cyanide-resistant respiration is correlated with a higher polarity of this compound as compared with CoQ2 and endogenous CoQ10 of mitochondria. The role of the polyisoprenoid substituent in CoQ10 as a structural component providing for the specificity of interaction with mitochondrial respiratory chain carriers is discussed.

Alkenes↗

[Dual center binding of cocarcinogens of the phorbol series with a receptor].

A systemic study based on literature data concerning the structure-activity relationships within a set of phorbol derivatives was carried out. Evidence in favour of the existence of two binding sites for phorbol derivatives on the receptor surface was obtained. The diterpenoid cycle binding site and the hydrophobic site for the binding of acyl hydrocarbon chains 12 and 13 were identified. The tumour-promoting effects of phorbol esters are due to their capability to simultaneously interact with the both sites of the receptor.

Caenorhabditis elegans Proteins↗

[Cumene hydroperoxide changes the type of conductivity of the mitochondrial membrane for K+].

The release of K+ from mitochondria under hypotonic conditions is a non-electrogenic process with an activity maximum at alkaline values of pH. Under these conditions an addition of cumene hydroperoxide causes the appearance of a second K+ release maximum at acidic pH values. The stimulation of K+ release by cumene hydroperoxide is accompanied by a decrease of the transmembrane potential and the accumulation of lipid peroxidation products. The effects of cumene hydroperoxide are prevented by the free radical scavenger, ionol. The acceleration of K+ release is not due to the activation of the non-electrogenic mechanism. It is concluded that the cumene hydroperoxide-induced release of K+ is caused by an increase in the nonspecific ionic permeability of the inner mitochondrial membrane and is controlled by free radical reactions. The contribution of K+ permeability of both types to the hormone-induced changes in the ionic composition of the mitochondrial matrix is discussed.

Animals↗

[Stimulation by quinones of cyanide-resistant respiration in rat liver and heart mitochondria].

It was shown that hydrophilic benzo- and naphthoquinones stimulate the cyanide-resistant respiration in liver and muscle mitochondria when succinate or NADH and glutamate or malate are used as oxidation substrates. The substrate-dependent oxygen uptake in the presence of cyanide is initiated by menadione, vicasol, 1.2-naphthoquinone, coenzyme Q0 and duroquinone. Rotenone and antimycin A do not inhibit the cyanide-resistant respiration. Oxidation of glutamate and malate in the course of CN-resistant respiration is inhibited by ortho- and bathophenanthroline and p-chloromercurybenzoate, whereas succinate oxidation by tenoyltrifluoroacetone, carboxin and pentachlorophenol. Superoxide dismutase, Cu2+ and catalase inhibit the CN-resistant respiration in the presence of quinones. Addition of catalase to the experimental cell causes O2 release.

Animals↗

[Unambiguous correspondence and complementarity of the chemical properties of amino acids and anticodons of the genetic code].

The chemical language of genetic code is proposed. As a result of chemical language application for the analysis of the modern genetic code, the existence of an unambiguous correspondence between the chemical properties of amino acids and their coding triplets (codons and anticodons) is shown. This confirms the hypothesis of the code chemical determination. The complementarity between the chemical properties of amino acids and their anticodons (but not the codons) has been found also to exist. This observation supports the hypothesis of the genetic code determination by the direct recognition and also underlines the primary role of anticodon in the origin of genetic code in comparison with codons.

Amino Acids↗

[Structure-activity relationship in the series of muscarinic acetylcholine receptor agonists: three types of agonist-receptor complexes].

A new procedure has been applied to analyze the data available in literature on the structure-activity relationships for agonists of the muscarinic acetylcholine receptor. The agonists were subdivided into three groups, each containing the compounds with the specific structural element. The binding constant logarithms, characterizing the agonist association with the receptor, increase linearly with the increase in the partition coefficient logarithms describing the distribution in the water-octanol system. The performed analysis suggests the existence of three different types of agonist-receptor complexes.

Animals↗

[Structure-activity relationship in the series of muscarinic acetylcholine receptor antagonists: four types of antagonist-receptor binding].

The data available in literature on the structure-activity relationships in the series of muscarinic antagonists have been analyzed. Three groups of the ammonium compounds are distinguished, each containing a specific chemical structure element. For the antagonist association with the receptor, the binding constant logarithms within each group depend linearly on the partition coefficient (pi) logarithms characterizing their distribution in the water-octanol system. The linear regression coefficients for pi are practically identical. A separate group consists of antagonists that have no ammonium grouping. Four possible modes of antagonist-receptor binding are surmized.

Animals↗

[Configuration and properties of a binding site for thyroid hormones on a specific receptor].

An analysis has been carried out of data available in literature on structure-function relationships for thyroid hormones, namely thyroxine, triiodothyronine and their analogues. The configuration and dimensions of the hormone-binding site of the receptor in a hormone-receptor complex are described. The receptor is shown to have a strained conformation in the complex. The analysis is indicative of the existence of two types of hormone-receptor complexes, a particular type being determined by the dimensions of analogues.

Binding Sites↗