Pub Date : 2025-02-26DOI: 10.1134/S0006350924700775
D. Y. Shtatnova, M. I. Kobyakova, Ya. V. Lomovskaya, E. I. Fetisova, K. S. Krasnov, R. S. Fadeev
In this study, the development process of drug resistance in acute lymphoblastic leukemia cells (Jurkat, MOLT 3, and MOLT 4 cell lines) was examined in high-density cell cultures. It has been shown that in high- density cultures of acute lymphoblastic leukemia cells resistance to the action of chemotherapeutic drugs in- creases comparing to the cells cultured under low-density conditions. The results obtained after investigation of the mechanism underlying increased drug resistance in acute lymphoblastic leukemia cells in high-density cell cultures showed that an increase in drug resistance in high-density cultures of cells can be mediated by a change in their proliferative activity. These findings can be applied in developing a strategy to overcome drug resistance in acute lymphoblastic leukemia cells, which depends on the density of the cell culture.
{"title":"Increased Drug Resistance in Acute lymphoblastic Leukemia Cells in Three-Dimensional High-Density Cell Cultures","authors":"D. Y. Shtatnova, M. I. Kobyakova, Ya. V. Lomovskaya, E. I. Fetisova, K. S. Krasnov, R. S. Fadeev","doi":"10.1134/S0006350924700775","DOIUrl":"10.1134/S0006350924700775","url":null,"abstract":"<p>In this study, the development process of drug resistance in acute lymphoblastic leukemia cells (Jurkat, MOLT 3, and MOLT 4 cell lines) was examined in high-density cell cultures. It has been shown that in high- density cultures of acute lymphoblastic leukemia cells resistance to the action of chemotherapeutic drugs in- creases comparing to the cells cultured under low-density conditions. The results obtained after investigation of the mechanism underlying increased drug resistance in acute lymphoblastic leukemia cells in high-density cell cultures showed that an increase in drug resistance in high-density cultures of cells can be mediated by a change in their proliferative activity. These findings can be applied in developing a strategy to overcome drug resistance in acute lymphoblastic leukemia cells, which depends on the density of the cell culture.</p>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"692 - 696"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S0006350924700787
V. G. Molchanov, A. Y. Yegorov, D. A. Osetrina, V. Yu. Novikov, N. M. Novojilov, A. A. Timchenko, E. A. Sogorin, M. A. Timchenko
During their long existence, crustaceans, despite the absence of a highly specific adaptive immune system, like vertebrates, have successfully adapted to survive in their natural habitat that is rich in microorganisms, in particular, due to antimicrobial peptides. One valuable source of antimicrobial peptides is the hepatopancreas (HPC), which is a waste product of crab fishing and processing. Using the method of zymography and 1H-NMR spectroscopy we found that an extract from the hepatopancreas of the snow crab contains a small peptide (about 3 kDa) that hydrolyzes the cell wall and polysaccharide of the cell wall of M. lysodeikticus. This peptide may be of interest for practical use. A protein (about 14 kDa) was isolated from the hepatopancreas of the Red king crab using heparin–sepharose chromatography, which also exhibits activity against the cell wall of the gram-positive bacterium M. lysodeikticus, as was shown by zymography and turbidimetry.
{"title":"Proteins of the Hepatopancreas of the Snow Crab and Red King Crab with Antibacterial Activity","authors":"V. G. Molchanov, A. Y. Yegorov, D. A. Osetrina, V. Yu. Novikov, N. M. Novojilov, A. A. Timchenko, E. A. Sogorin, M. A. Timchenko","doi":"10.1134/S0006350924700787","DOIUrl":"10.1134/S0006350924700787","url":null,"abstract":"<div><p>During their long existence, crustaceans, despite the absence of a highly specific adaptive immune system, like vertebrates, have successfully adapted to survive in their natural habitat that is rich in microorganisms, in particular, due to antimicrobial peptides. One valuable source of antimicrobial peptides is the hepatopancreas (HPC), which is a waste product of crab fishing and processing. Using the method of zymography and <sup>1</sup>H-NMR spectroscopy we found that an extract from the hepatopancreas of the snow crab contains a small peptide (about 3 kDa) that hydrolyzes the cell wall and polysaccharide of the cell wall of <i>M. lysodeikticus</i>. This peptide may be of interest for practical use. A protein (about 14 kDa) was isolated from the hepatopancreas of the Red king crab using heparin–sepharose chromatography, which also exhibits activity against the cell wall of the gram-positive bacterium <i>M. lysodeikticus</i>, as was shown by zymography and turbidimetry.</p></div>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"697 - 705"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S0006350924700684
Yu. S. Tarahovsky, S. G. Gaidin, Yu. A. Kim
Some aspects of the therapeutic effect of catechins are associated with their effect on the deposition of collagen fibrils in tissues. This process is believed to be under the control of the signaling and regulatory systems of cells affected by catechins, but the direct interaction of polyphenols with structural proteins cannot be excluded. In the present work, we investigated the direct effect of (+)-catechin and epigallocatechin gallate on the formation of collagen fibrils in vitro. Using turbidimetry, differential scanning calorimetry, and transmission electron microscopy, we have shown that (+)-catechin accelerates the formation of type I collagen fibrils, with the resulting fibrils having a protein-specific structure and thermal stability, whereas epigallocatechin gallate at a concentration of 10 μM inhibits fibrillogenesis. The obtained results expand our insights into possible mechanisms of therapeutic action of catechins, demonstrating the possibility of direct interaction of (+)-catechin and epigallocatechin gallate with collagen monomers and fibrils, and may be useful in the development of new drugs containing these plant polyphenols or their synthetic analogs.
{"title":"Effects of Catechins on the Formation of Collagen Fibrils In Vitro","authors":"Yu. S. Tarahovsky, S. G. Gaidin, Yu. A. Kim","doi":"10.1134/S0006350924700684","DOIUrl":"10.1134/S0006350924700684","url":null,"abstract":"<p>Some aspects of the therapeutic effect of catechins are associated with their effect on the deposition of collagen fibrils in tissues. This process is believed to be under the control of the signaling and regulatory systems of cells affected by catechins, but the direct interaction of polyphenols with structural proteins cannot be excluded. In the present work, we investigated the direct effect of (+)-catechin and epigallocatechin gallate on the formation of collagen fibrils <i>in vitro</i>. Using turbidimetry, differential scanning calorimetry, and transmission electron microscopy, we have shown that (+)-catechin accelerates the formation of type I collagen fibrils, with the resulting fibrils having a protein-specific structure and thermal stability, whereas epigallocatechin gallate at a concentration of 10 μM inhibits fibrillogenesis. The obtained results expand our insights into possible mechanisms of therapeutic action of catechins, demonstrating the possibility of direct interaction of (+)-catechin and epigallocatechin gallate with collagen monomers and fibrils, and may be useful in the development of new drugs containing these plant polyphenols or their synthetic analogs.</p>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"602 - 608"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S0006350924700751
P. M. Schwartsburd
This review analyzes the hypothesis of the preserved ability of various specialized mammalian cells to protect themselves from lethal injury by enacting a protective atavistic mechanism of cell dedifferentiation. The development of such a protection is accompanied by a transition of differentiated cells from the mitochondrial oxygen-dependent type of metabolism to reductive oxygen-independent metabolism (called the Warburg effect). This transition allows cells to increase the resistance to cell death from hypoxia, and can also induce the emergence of fetal markers characteristic of cell dedifferentiation. This paper, exemplified by the development of two pathologies (heart failure and type 2 diabetes), presents the findings that confirm the existence of such a mechanism and ways of its possible correction.
{"title":"Adaptive Self-Defense of Mature Cells against Damage Is Based on the Warburg Effect, Dedifferentiation of Cells, and Resistance to Cell Death","authors":"P. M. Schwartsburd","doi":"10.1134/S0006350924700751","DOIUrl":"10.1134/S0006350924700751","url":null,"abstract":"<p>This review analyzes the hypothesis of the preserved ability of various specialized mammalian cells to protect themselves from lethal injury by enacting a protective atavistic mechanism of cell dedifferentiation. The development of such a protection is accompanied by a transition of differentiated cells from the mitochondrial oxygen-dependent type of metabolism to reductive oxygen-independent metabolism (called the Warburg effect). This transition allows cells to increase the resistance to cell death from hypoxia, and can also induce the emergence of fetal markers characteristic of cell dedifferentiation. This paper, exemplified by the development of two pathologies (heart failure and type 2 diabetes), presents the findings that confirm the existence of such a mechanism and ways of its possible correction.</p>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"667 - 673"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S000635092470088X
G. R. Ivanitskii
A list of the author’s review papers with their summary is provided. They show the influence of biophysics on the development of life sciences. Biophysics, as a systems science, makes extensive use of mathematical modeling methods. Modeling results are important for both the theoretical development of biology and the development of applied sciences, biomedicine, gerontology, biosafety, and robotics.
{"title":"The Role of Biophysics in Modern Life Sciences","authors":"G. R. Ivanitskii","doi":"10.1134/S000635092470088X","DOIUrl":"10.1134/S000635092470088X","url":null,"abstract":"<div><p>A list of the author’s review papers with their summary is provided. They show the influence of biophysics on the development of life sciences. Biophysics, as a systems science, makes extensive use of mathematical modeling methods. Modeling results are important for both the theoretical development of biology and the development of applied sciences, biomedicine, gerontology, biosafety, and robotics.</p></div>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"803 - 810"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S0006350924700672
V. N. Antipova, A. K. Yunusova, R. I. Artyukh
Knowledge of the nature of intermolecular interactions and the amino-acid residues that provide them makes it possible to purposefully change the stability of intermolecular complexes. This study, using nickase Nt.BspD6I as an example, demonstrated the effect of hydrophobic interactions on a protein’s ability to oligomerize and the need for chemical and geometric complementarity of interface surfaces in the formation of stable homocomplexes.
{"title":"The Nature of Intermolecular Interactions Affecting Oligomerization of Nt.BspD6I Nickase","authors":"V. N. Antipova, A. K. Yunusova, R. I. Artyukh","doi":"10.1134/S0006350924700672","DOIUrl":"10.1134/S0006350924700672","url":null,"abstract":"<div><p>Knowledge of the nature of intermolecular interactions and the amino-acid residues that provide them makes it possible to purposefully change the stability of intermolecular complexes. This study, using nickase Nt.BspD6I as an example, demonstrated the effect of hydrophobic interactions on a protein’s ability to oligomerize and the need for chemical and geometric complementarity of interface surfaces in the formation of stable homocomplexes.</p></div>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"597 - 601"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S0006350924700805
M. H. Galimova, A. S. Averin
Regulation of the cardiovascular system in hypothermia and after its exposure is one of the important and urgent issues of biomedical research. This is due both to the severe consequences of hypothermia and to the potential benefits of its use for medical purposes. Adrenergic regulation is key for the normal functioning of the cardiovascular system. There are three groups of adrenergic receptors, α1, α2, and β, which are expressed in different proportions in the myocardium and blood vessels. Activation of each of the subtypes of adrenoreceptors can cause multidirectional effects, which are largely modified at low temperatures. The effectiveness of β-adrenergic stimulation decreases and can even act unidirectionally with hypothermia, leading to disorders in the work of the myocardium. The severity of the effects of α1-adrenoagonists in the heart and blood vessels also decreases; however, sensitivity to stimulation of α1a receptors in blood vessels may increase. Activation of this type of receptor has a cardioprotective effect. Activation of α2-adrenergic receptors also causes a wide range of cardioprotective effects. At the same time, there is evidence of direct inotropic and vascular effects mediated by this type of receptor. There is some evidence of an increase in these effects in hypothermia. The present review considers the current state of research on the effects of stimulation of certain types of adrenoreceptors in normal and hypothermic conditions. The mechanisms of physiological effects and the prospects for their further research are discussed.
{"title":"Adrenergic Regulation of Myocardial and Vascular Function in Hypothermia","authors":"M. H. Galimova, A. S. Averin","doi":"10.1134/S0006350924700805","DOIUrl":"10.1134/S0006350924700805","url":null,"abstract":"<div><p>Regulation of the cardiovascular system in hypothermia and after its exposure is one of the important and urgent issues of biomedical research. This is due both to the severe consequences of hypothermia and to the potential benefits of its use for medical purposes. Adrenergic regulation is key for the normal functioning of the cardiovascular system. There are three groups of adrenergic receptors, α1, α2, and β, which are expressed in different proportions in the myocardium and blood vessels. Activation of each of the subtypes of adrenoreceptors can cause multidirectional effects, which are largely modified at low temperatures. The effectiveness of β-adrenergic stimulation decreases and can even act unidirectionally with hypothermia, leading to disorders in the work of the myocardium. The severity of the effects of α1-adrenoagonists in the heart and blood vessels also decreases; however, sensitivity to stimulation of α1a receptors in blood vessels may increase. Activation of this type of receptor has a cardioprotective effect. Activation of α2-adrenergic receptors also causes a wide range of cardioprotective effects. At the same time, there is evidence of direct inotropic and vascular effects mediated by this type of receptor. There is some evidence of an increase in these effects in hypothermia. The present review considers the current state of research on the effects of stimulation of certain types of adrenoreceptors in normal and hypothermic conditions. The mechanisms of physiological effects and the prospects for their further research are discussed.</p></div>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"720 - 728"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S0006350924700854
O. M. Rozanova, T. A. Belyakova, E. N. Smirnova, S. S. Sorokina, A. R. Dyukina, A. E. Shemyakov, N. S. Strelnikova
The effect of proton radiation on the induction of cytogenetic damage in the bone marrow, the production of reactive oxygen species in whole blood, and the state of the thymus and spleen depending on linear energy transfer were studied during total irradiation of mice before the Bragg peak and at the peak in the dose range 0.1–1.5 Gy. It was found that the yield of polychromatophilic erythrocytes with micronuclei at all doses of proton radiation at the Bragg peak with a linear energy transfer of 2.5 keV/μm was close to the level of linear energy transfer with micronuclei for the corresponding doses of X-ray radiation with a linear energy transfer of 2.0 keV/μm; while when irradiated before the Bragg peak with a linear energy transfer of 0.7 keV/μm, the level of cytogenetic damage was significantly lower. The coefficient of relative biological effectiveness of proton irradiation calculated from the linear energy transfer by estimating micronuclei frequency at the Bragg peak was 1.15, and before the peak it was 0.63. Organ-specific differences in the patterns of pathophysiological effects were revealed, depending on the dose and linear energy transfer of protons on the thymus and spleen of mice, as well on the state of the antioxidant system of blood cells.
{"title":"Features of the Effects of Exposure to 90–170 MeV Proton Radiation on the Blood-Forming Organs in Mice under Total Irradiation with Proton Pencil Scanning Beam Depending on the Linear Energy Transfer of Particles","authors":"O. M. Rozanova, T. A. Belyakova, E. N. Smirnova, S. S. Sorokina, A. R. Dyukina, A. E. Shemyakov, N. S. Strelnikova","doi":"10.1134/S0006350924700854","DOIUrl":"10.1134/S0006350924700854","url":null,"abstract":"<div><p>The effect of proton radiation on the induction of cytogenetic damage in the bone marrow, the production of reactive oxygen species in whole blood, and the state of the thymus and spleen depending on linear energy transfer were studied during total irradiation of mice before the Bragg peak and at the peak in the dose range 0.1–1.5 Gy. It was found that the yield of polychromatophilic erythrocytes with micronuclei at all doses of proton radiation at the Bragg peak with a linear energy transfer of 2.5 keV/μm was close to the level of linear energy transfer with micronuclei for the corresponding doses of X-ray radiation with a linear energy transfer of 2.0 keV/μm; while when irradiated before the Bragg peak with a linear energy transfer of 0.7 keV/μm, the level of cytogenetic damage was significantly lower. The coefficient of relative biological effectiveness of proton irradiation calculated from the linear energy transfer by estimating micronuclei frequency at the Bragg peak was 1.15, and before the peak it was 0.63. Organ-specific differences in the patterns of pathophysiological effects were revealed, depending on the dose and linear energy transfer of protons on the thymus and spleen of mice, as well on the state of the antioxidant system of blood cells.</p></div>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"775 - 783"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S0006350924700878
T. A. Zenchenko, N. I. Khorseva, A. A. Stankevich
Studies of the phenomenology of the effect of synchronization of heart rate fluctuations in a person at rest with variations of the geomagnetic field in the range of 3–40 min periods have been continued. During 2012–2023, 508 experiments (lasting 100–120 min each) were conducted to monitor minute heart rate indicators in three practically healthy women (55, 45 and 30 years old). Individual experimental samples comprised 328, 113, and 67 records, respectively. It was shown that for each of the three volunteers, in about 60% of the experiments, the wavelet spectrum of heart rates turned out to be very close to the spectrum of synchronous variations of at least one of the horizontal components of the geomagnetic field (X or Y). As well, within the studied frequency range of 3–40 min, three sub-ranges were identified in which the degree of synchronicity of oscillation occurrence was maximum: 3.5 min, 10–12 min, and 33–36 min. It can be concluded that the effect of biogeosynchronization apparently did not occur uniformly over the entire range of 3–40 min, but mainly in these sub-ranges.
{"title":"The Effect of Synchronizing the Human Heart Rhythm with Geomagnetic Field Variations: Are There Particular Frequencies?","authors":"T. A. Zenchenko, N. I. Khorseva, A. A. Stankevich","doi":"10.1134/S0006350924700878","DOIUrl":"10.1134/S0006350924700878","url":null,"abstract":"<div><p>Studies of the phenomenology of the effect of synchronization of heart rate fluctuations in a person at rest with variations of the geomagnetic field in the range of 3–40 min periods have been continued. During 2012–2023, 508 experiments (lasting 100–120 min each) were conducted to monitor minute heart rate indicators in three practically healthy women (55, 45 and 30 years old). Individual experimental samples comprised 328, 113, and 67 records, respectively. It was shown that for each of the three volunteers, in about 60% of the experiments, the wavelet spectrum of heart rates turned out to be very close to the spectrum of synchronous variations of at least one of the horizontal components of the geomagnetic field (<i>X</i> or <i>Y</i>). As well, within the studied frequency range of 3–40 min, three sub-ranges were identified in which the degree of synchronicity of oscillation occurrence was maximum: 3.5 min, 10–12 min, and 33–36 min. It can be concluded that the effect of biogeosynchronization apparently did not occur uniformly over the entire range of 3–40 min, but mainly in these sub-ranges.</p></div>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"792 - 802"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-26DOI: 10.1134/S0006350924700714
A. I. Ilzorkina, N. V. Belosludtseva, A. A. Semenova, M. V. Dubinin, K. N. Belosludtsev
TRO19622 (olesoxime, a cholesterol-like cytoprotector) is an experimental drug developed for the potential therapy of a number of incurable degenerative diseases. The main molecular target of this compound in the cell is the porin proteins of the outer mitochondrial membrane, which play a key role in regulating the exchange of metabolites between mitochondria and the rest of the cell. Violations of the activity of these channels can cause the development of mitochondrial dysfunction in healthy cells. This paper evaluates the main indicators of mitochondrial functions and the cell viability index in cultures after their incubation with TRO19622. It was found that TRO19622 at concentrations of 15–30 μM inhibited the rates of phosphorylating and uncoupled respiration of isolated mitochondria (states 3 and 3UDNP) with succinate as a substrate, but did not affect the enzymatic activity of complexes I–IV of the respiratory chain. It was shown that TRO19622 in the studied doses did not affect the rate of H2O2 formation in mitochondria and the parameter of calcium capacity, reflecting the resistance of organelles to the opening of a calcium-dependent nonspecific pore. Incubation of human skin fibroblasts and breast adenocarcinoma cells (MCF-7) with 30 μM TRO19622 for 48 h had no effect on the production of reactive oxygen species and cell viability. The mechanisms of action of TRO19622 on the oxidative phosphorylation system and the prospects of using this mitochondrial-directed therapeutic agent are discussed.
{"title":"The Effect of TRO19622 (Olesoxime) on the Functional Activity of Isolated Mitochondria and Cell Viability","authors":"A. I. Ilzorkina, N. V. Belosludtseva, A. A. Semenova, M. V. Dubinin, K. N. Belosludtsev","doi":"10.1134/S0006350924700714","DOIUrl":"10.1134/S0006350924700714","url":null,"abstract":"<div><p>TRO19622 (olesoxime, a cholesterol-like cytoprotector) is an experimental drug developed for the potential therapy of a number of incurable degenerative diseases. The main molecular target of this compound in the cell is the porin proteins of the outer mitochondrial membrane, which play a key role in regulating the exchange of metabolites between mitochondria and the rest of the cell. Violations of the activity of these channels can cause the development of mitochondrial dysfunction in healthy cells. This paper evaluates the main indicators of mitochondrial functions and the cell viability index in cultures after their incubation with TRO19622. It was found that TRO19622 at concentrations of 15–30 μM inhibited the rates of phosphorylating and uncoupled respiration of isolated mitochondria (states 3 and 3UDNP) with succinate as a substrate, but did not affect the enzymatic activity of complexes I–IV of the respiratory chain. It was shown that TRO19622 in the studied doses did not affect the rate of H<sub>2</sub>O<sub>2</sub> formation in mitochondria and the parameter of calcium capacity, reflecting the resistance of organelles to the opening of a calcium-dependent nonspecific pore. Incubation of human skin fibroblasts and breast adenocarcinoma cells (MCF-7) with 30 μM TRO19622 for 48 h had no effect on the production of reactive oxygen species and cell viability. The mechanisms of action of TRO19622 on the oxidative phosphorylation system and the prospects of using this mitochondrial-directed therapeutic agent are discussed.</p></div>","PeriodicalId":493,"journal":{"name":"Biophysics","volume":"69 4","pages":"630 - 638"},"PeriodicalIF":4.033,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143496714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}