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Biomedical subjects

D B Zorov

Publications and source records attributed to D B Zorov.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Stimulation of mitochondrial respiration, induced by laser irradiation in the presence of rhodamine dyes].

The effect of micromolar concentration of rhodamine 123 (methylrhodamine) and ethyl and amyl esters of unsubstituted rhodamine on oxygen consumption by rat liver mitochondria was studied under irradiation by an argon laser (488 and 514 nm). Irradiation of mitochondria in the presence of rhodamine stimulates their respiration. Light-induced stimulation of respiration is not inhibited by free radical scavenger ionol and by inhibitor of the permeability transition pore cyclosporine A. Stimulation of respiration by moderate doses of radiation is reversed in the dark. Increase in radiation dose resulted in only partial reversal of stimulated respiration in the dark. Rhodamine efficacy in stimulation of mitochondrial respiration depends on its structure (amyl > ethyl > methylrhodamine).

Animals↗
PubMed1996

[Mitochondrial transport of nucleic acids. Participation of the benzodiazepine receptor].

The models of mitochondrial transmembrane nucleic acid transfer are discussed. According to this hypothesis, mitochondria can exchange their nucleic acids by two possible mechanisms including either intermitochondrial fusion and fission or transmembrane transport. In the latter case, important roles for mitochondrial benzodiazepine receptor and factors that regulate activities of its components (mitochondrial porin and adenine nucleotide translocator) are suggested. Nucleic acids can be transported through a Ca(2+)-dependent pore that can be one of the functional states of mitochondrial exchange of genetic material. Problems like cellular aging, apoptosis, proliferation, mitochondrial diseases, multidrug resistance, intracellular traffic, and mitochondrial heredity are discussed considering an important role of mitochondrial benzodiazepine receptor in these processes.

Biological Transport↗
PubMed1995

Immunoelectron microscopic study of the distribution of porin on outer membranes of rat heart mitochondria.

The distribution of porin on the outer membranes of rat heart mitochondria has been studied by means of immunogold labelling with antibodies to the N-terminal part of the human protein. It was found that only a minority of isolated, unfixed mitochondria are labelled by these antibodies, with the gold particles frequently organized in threads or bands. Extensive immunogold labelling is frequently observed on regions of outer membranes stripped away from mitochondria and on regions separating two mitochondrial compartments whose cristae display different configurations (possibly representing two mitoplasts covered by a common outer membrane). Also, pairs of connected mitochondria are sometimes heavily labelled in the "neck" regions, which may represent the junctions involved in electrical communication between mitochondria in cardiac tissue.

Animals↗
PubMed1994

[Detection of porin in inter-mitochondrial contacts].

The binding of monoclonal antibodies (mAb) to the N-terminal part of VDAC with freshly isolated, unfixed rat heart mitochondria has been studied. It was established that mAb do not react with the main portion of the mitochondria. At the same time, successful binding to some of those was observed. Gold particles were organized, as a rule in three types of clusters: (i) thread-like clusters; (ii) small, irregularly shaped clusters, and (iii) big clusters covering the greater part of the mitochondrial surface. In the region of tight junctions between mitochondria, specific binding of mAb to mitochondrial VDAC, such as thread-like and small clusters, was found. In some cases, antibody clusters were localized in the region which separates two mitochondrial compartments differing in configuration of the cristae. When the outer mitochondrial membrane was partially stripped off, this membrane was extensively labelled by antibodies. It is concluded that the N-terminus of porin is localized on the inner surface of the outer mitochondrial membrane, so that some damage of the outer membrane appears to be required to allow the N-terminal porin antibody to contact the antigenic determinant. Such a damage is apparently more probable in the place of contacts of two mitochondria or two mitoplasts covered by the common outer membrane. In any case, the data obtained strongly suggest that porin is present in the junction region.

Animals↗
PubMed1993

Mitochondrial benzodiazepine receptor linked to inner membrane ion channels by nanomolar actions of ligands.

The mitochrondrial benzodiazepine receptor (mBzR) binds a subset of benzodiazepines and isoquinoline carboxamides with nanomolar affinity and consists of the voltage-dependent anion channel, the adenine nucleotide translocator, and an 18-kDa protein. The effect of ligands of the mBzR on two inner mitochondrial membrane channel activities was determined with patch-clamp techniques. The relative inhibitory potencies of the drugs resemble their binding affinities for the mBzR. Ro5-4864 and protoporphyrin IX inhibit activity of the multiple conductance channel (MCC) and the mitochondrial centum-picosiemen (mCtS) channel activities at nanomolar concentrations. PK11195 inhibits mCtS activity at similar levels. Higher concentrations of protoporphyrin IX induce MCC but possibly not mCtS activity. Clonazepam, which has low affinity for mBzR, is at least 500 times less potent at both channel activities. Ro15-1788, which also has a low mBzR affinity, inhibits MCC at very high concentrations (16 microM). The findings indicate an association of these two channel activities with the proteins forming the mBzR complex and are consistent with an interaction of inner and outer membrane channels.

Animals↗
PubMed1992

Multiple conductance levels in rat heart inner mitochondrial membranes studied by patch clamping.

The behavior of the mitochondrial inner membrane multiple conductance channel (MCC) which has a peak conductance of 1-1.5 nS has been examined in rat heart mitochondria. MCC can display several unique characteristics: (a) prolonged open and closed times on the order of seconds to minutes, (b) a voltage dependence in which MCC opens (negative potential) or closes (positive potential) generally in steps, (c) a response to inhibitors such as amiodarone in steps corresponding at least approximately to those in (b), (d) a 'free-running mode' in which the current level rapidly fluctuates between a minimum of nine conductance levels but with a preferred occupation of the 0.5-0.7 nS levels, and (e) very large transitions (1-1.5 nS) resolved at 4 kHz bandwidth as single events with variable mean open time.

Animals↗
PubMed1992

Modulation of inner mitochondrial membrane channel activity.

Three classes of inner mitochondrial membrane (IMM) channel activities have been defined by direct measurement of conductance levels in membranes with patch clamp techniques in 150 mM KCl. The "107 pS activity" is slightly anion selective and voltage dependent (open with matrix positive potentials). "Multiple conductance channel" (MCC) activity includes several levels from about 40 to over 1000 pS and can be activated by voltage or Ca2+. MCC may be responsible for the Ca(2+)-induced permeability transition observed with mitochondrial suspensions. A "low conductance channel" (LCC) is activated by alkaline pH and inhibited by Mg2+. LCC has a unit conductance of about 15 pS and may correspond to the inner membrane anion channel, IMAC, which was proposed from the results obtained from suspension studies. All of the IMM channels defined thus far appear to be highly regulated and have a low open probability under physiological conditions. A summary of what is known about IMM channel regulation and pharmacology is presented and possible physiological roles of these channels are discussed.

Animals↗
PubMed1992

Voltage activation of heart inner mitochondrial membrane channels.

The patch clamp records obtained from mitoplast membranes prepared in the presence of a calcium chelator generally lack channel activity. However, multiconductance channel (MCC) activity can be induced by membrane potentials above +/- 60 mV [Kinnally et al., Biochem. Biophys. Res. Commun. 176, 1183-1188 (1991)]. Once activated, the MCC activity persists at all voltages. The present report characterizes the activation by voltage of multiconductance channels of rat heart inner mitochondrial membranes using patch-clamping. In some membrane patches, the size of single current transitions progressively increases with time upon application of voltage. The inhibitor cyclosporin has also been found to decrease channel conductance in steps. The results suggest that voltage-induced effects which are inhibited by cyclosporin A are likely to involve either an increase in effective pore diameter or the assembly of low-conductance units. In activated patches, we have found at high membrane potentials (e.g., 130 mV) changes in conductance as high as 5 nS occurring in large steps (up to 2.7 nS). These were generally preceded by a smaller transition. Similar results were obtained less frequently at lower voltages. These results can be explained on the assumption that once assembled the channels may act in unison.

Animals↗
PubMed1991

Effects of amyl ester of unsubstituted rhodamine on respiration and Ca2+ transport in rat liver mitochondria.

In rat liver mitochondria the amylrhodamine is responsible for uncoupling (respiratory stimulation in state 4) by two distinct processes. Immediately after amylrhodamine addition (2-12 microM) stimulation of respiration takes place. Respiration rate for this phase is constant in time, it is independent of the potassium or inorganic phosphate content in the medium, not inhibited by oligomycin, ruthenium red, cyclosporine A, N-ethyl-maleimide and EGTA. The second phase of the respiratory stimulation is not linear in time. Respiration rate within this phase increases with rising of potassium and phosphate content in the medium. This effect is abolished by oligomycin, ruthenium red, cyclosporine A, N-ethylmaleimide and EGTA. The beginning of respiratory increment coincides with the second phase of Ca2+ release from mitochondria.

Animals↗
PubMed1991

[Properties of mitochondrial porin from cattle heart].

Porin, a protein able to form ionic channels in model phospholipid membranes, has been isolated for the first time from bovine heart mitochondria. One-dimensional electrophoresis in the presence of sodium dodecyl sulfate revealed a major band with Mr of 32-34 kDa. On two-dimensional electrophoregrams this protein is represented by four components with pI ranging from 6.5 to 7.1. Porin spots were identified on two-dimensional electrophoregrams in a complete mixture of mitochondrial proteins. The presence of porin in bovine heart submitochondrial particles was demonstrated by two-dimensional electrophoresis.

Animals↗
PubMed1991

[The effect of cyclosporin A and oligomycin on the nonspecific permeability of the mitochondria inner membrane].

The effect of oligomycin and cyclosporine A on Ca(2+)-induced nonspecific permeability of the inner mitochondrial membrane was under study. Both oligomycin and cyclosporine A were able to prevent the activation of nonspecific permeability; however, but cyclosporine A was the only agent which could restore the initial permeability of the inner mitochondrial membrane. The effect of cyclosporine A was not shown to be mediated through redistribution of Ca2+ ions between different subpopulations of mitochondria.

Animals↗
PubMed1991

[The role of the ADP/ATP-antiporter in the inhibition of nonspecific permeability of the inner mitochondrial membrane by cyclosporin A].

The effect of the conformational state of the ADP/ATP-antiporter on the efficiency of inhibition by cyclosporine A of the Ca(2+)-induced increase of nonspecific permeability of the inner mitochondrial membrane was under study. It was found that the ADP/ATP-antiporter inhibitor carboxyatractyloside is able to reverse the cyclosporine A-induced inhibition of this nonspecific permeability. The effect of carbocyatractyloside is manifested only in mitochondria depleted of adenine nucleotides. The bifunctional SH-reagent phenylarsine oxide is also able to reverse the cyclosporine A effect. The data obtained testify to the fact that inhibition by cyclosporine A of nonspecific permeability is due to its effect on the conformational state of the ADP/ATP-antiporter.

Arsenicals↗
PubMed1990

Effect of ADP/ATP antiporter conformational state on the suppression of the nonspecific permeability of the inner mitochondrial membrane by cyclosporine A.

The influence of the conformational state of ADP/ATP antiporter on the efficiency of the inhibitory effect of cyclosporine A on the Ca2(+)-induced nonspecific permeability of the inner mitochondrial membrane has been studied. Carboxyatractiloside, the inhibitor of ADP/ATP-antiporter, was shown to prevent the cyclosporine A-induced suppression of the nonspecific permeability. The carboxyatractiloside effect was displayed only in mitochondria depleted of adenine nucleotides. Bifunctional SH reagent, phenylarsine oxide, was also able to reverse the effect of cyclosporine A. The data are consistent with the suggestion that cyclosporine A causes suppression of the nonspecific permeability due to its effect on the ADP/ATP antiporter conformation.

Animals↗
PubMed1990

Effect of cyclosporine A and oligomycin on non-specific permeability of the inner mitochondrial membrane.

The effect of oligomycin and cyclosporine A on the induction of non-specific permeability of the inner mitochondrial membrane by Ca2+ was under study. Both oligomycin and cyclosporine A were able to prevent the activation of non-specific permeability, but cyclosporine A was the only agent which could restore initial permeability of the inner mitochondrial membrane. The effect of cyclosporine A was shown not to be mediated through redistribution of Ca2+ between different mitochondrial subpopulations.

Animals↗
PubMed1988

Coupling membranes as energy-transmitting cables. I. Filamentous mitochondria in fibroblasts and mitochondrial clusters in cardiomyocytes.

An hypothesis considering mitochondria as intracellular power-transmitting protonic cables was tested in human fibroblasts where mitochondria are thin and long and in rat cardiomyocytes where they show cluster organization. Mitochondria in the cell were specifically stained with fluorescent-penetrating cation ethylrhodamine, which electrophoretically accumulates in the mitochondrial matrix. A 40-micron-long mitochondrial filament of fibroblast was illuminated by a very narrow (less than or equal to 0.5 micron) laser beam to induce local damage of the mitochondrial membranes. Such a treatment was found to induce quenching of the ethylrhodamine fluorescence in the entire filament. According to the electron microscope examination, the laser-treated filament retained its continuity after the laser illumination. Other mitochondrial filaments (some of which were localized at a distance less than 10 micron from the laser-treated one) remained fluorescent. In a cell where mitochondrial filaments seemed to be united in a network, laser illumination of one filament resulted in fluorescence quenching in the whole network, whereas fluorescence of small mitochondria not connected with the network was unaffected. The illumination of cardiomyocyte was found to result in the fluorescence quenching not only in a laser-illuminated mitochondrion but also in a large cluster of organelles composed of many mitochondria. Electron microscopy showed that all the mitochondria in the cluster change from the orthodox to the condensed state. It was also found that mitochondria in the cluster are connected to one another with specific junctions. If a mitochondrion did not form junctions with a quenched cluster, its fluorescence was not decreased even when this mitochondrion was localized close to an illuminated one. The size of the mitochondrial cluster may be as long as 50 micron. The cluster is formed by branched chains of contacting mitochondria, which may be defined as Streptio mitochondriale. In the cardiomyocyte there are several mitochondrial clusters or, alternatively, the quenched cluster is a result of decomposition of a supercluster uniting all the mitochondria of the cell. Cluster organization of mitochondria could also be revealed when a single mitochondrion was punctured in situ with a microcapillary. The obtained data are in agreement with the idea that mitochondrial junctions are H+ permeable so that, within the cluster, delta psi may be transmitted from one mitochondrion to another. The above results are consistent with the assumption that mitochondrial filaments or networks represent a united electrical system.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗