Vol 88, No 11 (2023)
Articles
Editorial
Abstract
Номер посвящён памяти яркого учёного-геронтолога Алексея Матвеевича Оловникова, чьи теоретические работы об укорочении теломер лежали у истоков нового направления науки - молекулярной биологии старения. Алексей Матвеевич был членом редакционной коллегии журнала; с его лёгкой руки журнал стал регулярно публиковать статьи геронтологической тематики. Начало этой традиции положил номер, полностью посвященный проблемам старения и укорочению теломер, авторами которого были ведущие мировые специалисты в этой области, откликнувшиеся на приглашение Алексея Матвеевича (№ 11, 1997).
Biochemistry. 2023;88(11):2037-2037
2037-2037
“If i were in nature’s place, i would do it like this...”. Life and hypotheses of Alexey Olovnikov
Abstract
In this article, we commemorate the life and scientific journey of the brilliant gerontologist-theorist Alexey Olovnikov (1936-2022). In 1971, he published his famous “marginotomy” hypothesis, in which he predicted the replicative shortening of telomeres and its role as a counter of cell divisions and biological age of an organism. This work put forth several remarkable assumptions, including the existence of telomerase, which were confirmed two decades later. Despite this, Alexey Olovnikov moved further in his theoretical studies of aging and proposed a series of new hypotheses that seem no less exotic than the marginotomy hypothesis once appeared. Alexey Olovnikov had an extraordinary way of looking at biological problems and, in addition to aging, authored striking concepts about development, biorhythms, and evolution.
Biochemistry. 2023;88(11):2038-2050
2038-2050
Relationships among development, growth, body size, reproduction, aging, and longevity - trade-offs and pace-of-life
Abstract
Relationships of growth, metabolism, reproduction, and body size to the biological process of aging and longevity have been studied for decades and various unifying “theories of aging” have been proposed to account for the observed associations. In general, fast development, early sexual maturation leading to early reproductive effort, as well as production of many offspring, have been linked to shorter lifespans. The relationship of adult body size to longevity includes a remarkable contrast between the positive correlation in comparisons between different species and the negative correlation seen in comparisons of individuals within the same species. We now propose that longevity and presumably also the rate of aging are related to the “pace-of-life.” A slow pace-of-life including slow growth, late sexual maturation, and a small number of offspring, predicts slow aging and long life. The fast pace of life (rapid growth, early sexual maturation, and major reproductive effort) is associated with faster aging and shorter life, presumably due to underlying trade-offs. The proposed relationships between the pace-of-life and longevity apply to both inter- and intra-species comparisons as well as to dietary, genetic, and pharmacological interventions that extend life and to evidence for early life programming of the trajectory of aging. Although available evidence suggests the causality of at least some of these associations, much further work will be needed to verify this interpretation and to identify mechanisms that are responsible.
Biochemistry. 2023;88(11):2051-2065
2051-2065
Olovnikov, telomeres and telomerase. is it possible to prolong a healthy life?
Abstract
The science of telomeres and telomerase has made tremendous progress in recent decades. In this review, we consider it first in a historical context (the Carrel-Hayflick-Olovnikov-Blackburn chain of discoveries) and then review current knowledge of telomere structure and dynamics in norm and pathology. Central to the review are the consequences of telomere shortening, including telomere position effects, DNA damage signaling, and increased genetic instability. Cell senescence and the role of telomere length in its development are discussed separately. Therapeutic aspects and risks of telomerase and other telomere lengthening methods are also discussed.
Biochemistry. 2023;88(11):2066-2083
2066-2083
Unstable DNA in neurons: counter of the life span and a driver of evolution
Abstract
The data on postmitotic instability of neuronal DNA, which have been reported in the last decade, are changing the theoretical landscape not only of neuroscience, but more broadly, of biology. A. M. Olovnikov suggested in 2003 that it is the DNA of neurons that can be the “initial substrate of aging”. The current data significantly increases the likelihood of this hypothesis. How does neuronal DNA accumulate damage, in what regions of the genome, what factors contribute to its accumulation, and how can they be associated with aging and the life span? These questions will be considered in the review. In addition, instability of the neuronal DNA had apparently been accompanied by a search for various ways to reduce the biological costs of brain function in Metazoan evolution. Phenomena such as sleep, an increase in the number of neurons in the vertebrate brain evolution, adult neurogenesis, distributed neuronal activity, somatic polyploidy, RNA editing in cephalopods can be reconsidered in the light of “DNA plasticity-instability trade-off” in neurons. The topic is of obvious importance not only for fundamental neuroscience, but also for translational medicine.
Biochemistry. 2023;88(11):2084-2100
2084-2100
Potential geroprotectors - from the banch to the clinic
Abstract
Geroprotectors are substances that slow down the aging process and can be used in the prevention of age-related diseases. Geroprotectors can improve the functioning of various organ systems and enhance their homeostatic capabilities. We have developed a system of criteria for geroprotectors and proposed their classification based on the mechanisms of action on the aging processes. It is necessary for geroprotectors to reduce mortality, improve human aging biomarkers, have minimal side effects, and enhance quality of life. Additionally, there are approaches based on combining geroprotectors targeted at different targets and mechanisms of aging to achieve maximum effectiveness. Currently, numerous preclinical studies are being conducted to identify new molecular targets and develop new approaches to extend healthy aging, although the number of clinical trials is limited. Geroprotectors have the potential to become a new class of preventive medicines as they prevent the onset of certain diseases or slow down their progression.
Biochemistry. 2023;88(11):2101-2108
2101-2108
Retrotransposons and telomeres
Abstract
Transposable elements (TEs) comprise a significant part of eukaryotic genomes being a major source of genome instability and mutagenesis. Cellular defense systems suppress the TE expansion at all stages of their life cycle. Piwi proteins and Piwi-interacting RNAs (piRNAs) are key elements of the anti-transposon defense system, which control TE activity in metazoan gonads preventing inheritable transpositions and developmental defects. In this review, we discuss various regulatory mechanisms by which small RNAs combat TE activity. However, active transposons persist, suggesting these powerful anti-transposon defense mechanisms have a limited capacity. A growing body of evidence suggests that increased TE activity coincides with genome reprogramming and telomere lengthening in different species. In the Drosophila fruit fly, whose telomeres consist only of retrotransposons, a piRNA-mediated mechanism is required for telomere maintenance and their length control. Therefore, the efficacy of protective mechanisms must be finely balanced in order not only to suppress the activity of transposons, but also to maintain the proper length and stability of telomeres. Structural and functional relationship between the telomere homeostasis and LINE1 retrotransposon in human cells indicates a close link between selfish TEs and the vital structure of the genome, telomeres. This relationship, which permits the retention of active TEs in the genome, is reportedly a legacy of the retrotransposon origin of telomeres. The maintenance of telomeres and the execution of other crucial roles that TEs acquired during the process of their domestication in the genome serve as a type of payment for such a “service.”
Biochemistry. 2023;88(11):2109-2126
2109-2126
To be mobile or not: the variety of reverse transcriptases and their recruitment by host genomes
Abstract
Reverse transcriptases (RT), or RNA-dependent DNA polymerases, are unorthodox enzymes that originally added a new angle to the conventional view of the unidirectional flow of genetic information in the cell from DNA to RNA to protein. First discovered in vertebrate retroviruses, RTs were since re-discovered in most eukaryotes, bacteria, and archaea, spanning essentially all domains of life. For retroviruses, RTs provide the ability to copy the RNA genome into DNA for subsequent incorporation into the host genome, which is essential for their replication and survival. In cellular organisms, most RT sequences originate from retrotransposons, the type of self-replicating genetic elements that rely on reverse transcription to copy and paste their sequences into new genomic locations. Some retroelements, however, can undergo domestication, eventually becoming a valuable addition to the overall repertoire of cellular enzymes. They can be beneficial yet accessory, like the diversity-generating elements, or even essential, like the telomerase reverse transcriptases. Nowadays, ever-increasing numbers of domesticated RT-carrying genetic elements are being discovered. It may be argued that domesticated RTs and reverse transcription in general is more widespread in cellular organisms than previously thought, and that many important cellular functions, such as chromosome end maintenance, may evolve from an originally selfish process of converting RNA into DNA.
Biochemistry. 2023;88(11):2127-2137
2127-2137
Microgravity effects and aging physiology: similar changes or common mechanisms?
Abstract
Despite the use of preventive measures (including intense physical activity), cosmonauts and astronauts develop muscle atony and atrophy, insufficiency of the cardiovascular system, osteopenia, etc. All these changes, reminiscent of age-related physiological changes, occur in a healthy person in microgravity quite quickly - within a few months. Adaptation to the absence of gravity leads to the symptoms of aging, which are compensated after returning to Earth. The prospect of interplanetary flights raises the question of gravity thresholds, below which the main physiological systems will lose their functional potential, similar to aging, and affect life expectancy. An important role in the aging process belongs to the body’s cellular reserve - progenitor cells, which are involved in physiological remodeling and regenerative/reparative processes of all physiological systems. With age, progenitor cell count and the regenerative potential decreases. Moreover, their paracrine spectrum becomes pro-inflammatory during replicative senescence, disrupting tissue homeostasis. Mesenchymal stem/stromal cells (MSCs) are mechanosensitive, and therefore the absence of a gravitational stimulus causes serious changes in their functional status. The review compares the cellular effects of microgravity and changes developing in senescent cells, including stromal precursors.
Biochemistry. 2023;88(11):2138-2155
2138-2155
Actuarial aging rates in human cohorts
Abstract
Aging rate is an important characteristic of human aging. Attempts to measure aging rates through the Gompertz slope parameter lead to a conclusion that actuarial aging rates were stable during the most of the 20th century, but recently demonstrate an increase over time in the majority of studied populations. These findings were made using cross-sectional mortality data rather than by the analysis of mortality of real birth cohorts. In this study we analyzed historical changes of actuarial aging rates in human cohorts. The Gompertz parameters were estimated in the age interval 50-80 years using data on one-year cohort age-specific death rates from the Human Mortality Database (HMD). Totally, data for 2,294 cohorts of men and women from 76 populations were analyzed. Changes of the Gompertz slope parameter in the studied cohorts revealed two distinct patterns for actuarial aging rate. In higher mortality Eastern European countries actuarial aging rates showed continuous decline from the 1910 to 1940 birth cohort. In lower mortality Western European countries, Australia, Canada, Japan, New Zealand, and USA actuarial aging rates declined from the 1910th to approximately 1930th cohort and then increased. Overall, in 50 out of 76 populations (68%) actuarial aging rate demonstrated decreasing pattern of change over time. Compensation effect of mortality (CEM) was tested for the first time in human cohorts and the cohort species-specific lifespan was estimated. CEM was confirmed using cohort data and human cohort species-specific lifespan estimates were similar to the estimates obtained for the cross-sectional data published earlier.
Biochemistry. 2023;88(11):2156-2165
2156-2165
Regular articles
A solitary stalled 80S ribosome prevents mRNA recruitment to stress granules
Abstract
In response to stress stimuli, eukaryotic cells typically suppress protein synthesis. This leads to the mRNA release from polysomes, their condensation with RNA-binding proteins, and the formation of non-membrane-bound cytoplasmic compartments called stress granules (SGs). SGs contain 40S but generally lack 60S ribosomal subunits. It is known that cycloheximide, emetine, and anisomycin, the ribosome inhibitors which block the 80S ribosome progression along mRNA and stabilize polysomes, prevent SG assembly. Conversely, puromycin, which induces premature termination, releases mRNAs from polysomes and stimulates the formation of SGs. The same effect is caused by some translation initiation inhibitors, which lead to polysome disassembly and the accumulation of mRNAs in a form of stalled 48S preinitiation complexes. Based on these and other data, it is believed that the trigger for SG formation is the presence of mRNA with extended ribosome-free segments, which tend to form condensates in the cell. In this study, we evaluated the ability of various small-molecule translation inhibitors to block or stimulate the assembly of SGs under conditions of severe oxidative stress induced by sodium arsenite. Contrary to expectations, we found that ribosome-targeting elongation inhibitors of a specific type, that arrest solitary 80S ribosomes at the beginning of the mRNA coding regions but do not interfere with all subsequent ribosomes in completing translation and leaving the transcripts (such as harringtonine, lactimidomycin, or T-2 toxin), completely prevented the formation of arsenite-induced SGs. These observations suggest that the presence of even a single 80S ribosome on mRNA is sufficient to prevent its recruitment into SGs, and the presence of extended ribosome-free regions of mRNA is not sufficient for SG formation. We propose that mRNA entry into SGs may be mediated by specific contacts between RNA-binding proteins and those regions on 40S subunits that remain inaccessible when ribosomes are associated.
Biochemistry. 2023;88(11):2166-2182
2166-2182
Peptide carriers as delivery vehicles for therapeutic nucleic acids. Мechanisms and potential applications in medicine
Abstract
Currently, a significant number of drugs based on therapeutic nucleic acids are being under development for the treatment of oncological, inflammatory, infectious diseases, and metabolic disorders. A growing number of approved nucleic acid therapeutics demonstrate the potential of gene therapy approaches. Therapeutic nucleic acids realize their biological effect in the cytoplasm, while plasma membrane is the main barrier to their intracellular delivery. Therefore, specially designed carriers are often used during the development of such drugs. The optimal carrier should not only facilitate the internalization of nucleic acids, but also exhibit no toxic effects, provide stabilization, and must be suitable for large scale production at low cost. Cell penetrating peptides (CPPs) match all these requirements. CPPs are effective and low-toxic carriers of nucleic acids. They usually represent basic peptides with a positive charge at physiological pH that capable to form nanostructures with negatively charged nucleic acids. Numerous preclinical studies in which CPP has been used as a carrier have shown promising results. In some cases, CPP-containing drugs successfully passed through clinical trials and the implemented into clinical practice. In this review, we consider the variety of therapeutic nucleic acids and summarize the experience of using CPP for their intracellular delivery. In addition, the classification and mechanisms of CPP cellular uptake are discussed, the understanding of which will accelerate the development of new gene therapy drugs.
Biochemistry. 2023;88(11):2183-2205
2183-2205
Immune privileges as a result of mutual regulation of the immune and stem systems
Abstract
The immune privileges of cancer stem cells are a well-known and widely studied problem, as the presence of such cells in tumors is associated with refractoriness, recurrence, and metastasis. Accumulating evidence also suggests the presence of immune privileges for non-pathologic stem cells in addition to their other defense mechanisms against damaging factors. This similarity between pathologic and normal stem cells raises the question of why stem cells have such a potentially damaging property. The regulation of vital processes of autoimmunity control and regeneration by interactions between immune cells, stem cells and their microenvironment are reviewed as determinants of stem cell immune privilege formation. A deep mutual integration in the regulation of stem and immune cells is noted. Based on the diversity and complexity of the mutual regulation of stem cells, their microenvironment and the immune system, I propose to use the term “stem system”.
Biochemistry. 2023;88(11):2206-2220
2206-2220
Diversity and evolution of mitochondrial translation apparatus
Abstract
The evolution of mitochondria proceeded independently in different eukaryotic lines, reflected in the diversity of mitochondrial genomes and mechanisms of their expression observed in different eukaryotic species. Mitochondria lost most of the genes of their bacterial ancestor, partially transferred them to the nucleus or completely eliminated. However, the mitochondria of almost all eukaryotic cells retain relatively small genomes, as well as their replication, transcription, and translation apparatuses. Dependence on the nuclear genome, features of mitochondrial transcripts, and the necessity to synthesize highly hydrophobic membrane proteins led to a number of significant changes in translation apparatus derived from the bacterial ancestor. It retained the basic structure necessary for protein synthesis but became more specialized and labile. In this review, we consider what changes take place during the initiation of mitochondrial translation, and how the evolution of mitochondria affected the functions of the main factors initiating protein biosynthesis in these organelles.
Biochemistry. 2023;88(11):2221-2234
2221-2234
Nucleotide excision repair. Methods of determination the efficiency functioning
Abstract
The nucleotide excision repair (NER) system is responsible for removing a wide range of bulky damages from DNA, making a significant contribution to maintaining the stability of the genome. The efficiency with which the proteins of the NER system recognize and remove bulky damages depends on many factors and has important clinical and diagnostic significance. The review examines the current understanding of the molecular basis of the functioning of the NER system in eukaryotic cells, as well as analyzes the methods and approaches that are used to study the efficiency functioning of this DNA repair system both in vitro and ex vivo.
Biochemistry. 2023;88(11):2235-2250
2235-2250
T-Lymphocyte metabolic features and techniques to modulate them
Abstract
T cells demonstrate a high degree of complexity and a broad range of functions which distinguish them from other immune cells. Throughout life, T lymphocytes experience several functional states: quiescence, activation, proliferation, differentiation, performance of effector and regulatory functions, memory formation, and apoptosis. Metabolism supports all the T cell functions, providing lymphocytes with energy, biosynthetic substrates, and signaling molecules. Therefore, T cells usually restructure their metabolism as they transition from one functional state to another. The strong association between metabolism and T cell function implies that the immune response can be controlled by manipulating metabolic processes within T lymphocytes. This review aims to highlight the main metabolic adaptations necessary for T cell function, as well as the recent progress in techniques to modulate the lymphocyte metabolic features.
Biochemistry. 2023;88(11):2251-2270
2251-2270
Apelin C-terminal fragments: biological properties and therapeutic potential
Abstract
The creation of bioactive molecules for the treatment of cardiovascular diseases based on natural peptides stimulates intensive experimental research. In recent years, it has been established that the C-terminal fragments of apelin, an endogenous ligand of the APJ receptor, reduce metabolic and functional disorders in experimental heart damage. The review presents literature data and generalized results of our own experiments on the effect of apelin-13, [Pyr]apelin-13, apelin-12, and their chemically modified analogues on the heart in normal conditions and when modeling pathophysiological conditions in vitro and in vivo. It has been shown that the spectrum of action of apelin peptides on the damaged myocardium covers a decrease in the death of cardiomyocytes from necrosis, a decrease in cardiomyocyte membrane damage, an improvement in the metabolic state of the myocardium, and a decrease in the formation of reactive oxygen species and lipid peroxidation products. The mechanisms of the protective action of these peptides associated with the activation of the APJ receptor and the manifestation of antioxidant properties are discussed. The data presented in the review indicate the promise of molecular design of pharmacological APJ receptor agonists, which can serve as the basis for the development of cardioprotectors that affect the processes of free radical oxidation and metabolic adaptation.
Biochemistry. 2023;88(11):2271-2288
2271-2288
Pathological correlates of cognitive decline in Parkinson’s disease: from molecules to neural networks
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder resulting from the death of dopaminergic neurons in the substantia nigra and the appearance of protein aggregates in neuronal cell bodies composed predominantly of alpha-synuclein, known as Lewy bodies. PD is now recognized as a multisystem disorder characterized by severe motor impairment and various non-motor symptoms. Cognitive decline is one of the most common and worrisome non-motor symptoms. Moderate cognitive impairment (CI), diagnosed already in the early stages of PD, usually leads to deep dementia. The main types of CI observed in PD include executive dysfunction, attention, and memory disfunction, visuospatial decline, and verbal deficits. According to the literature, the following mechanisms play a significant role in the development of cognitive dysfunctions in PD: (1) changes in the conformational structure of synaptic proteins; (2) disruption of synaptic transmission; (3) neuroinflammation (pathological activation of neuroglia); (4) mitochondrial dysfunction and oxidative stress; (5) metabolic conditions; (6) functional remodeling of the neural networks. The listed molecular and synaptic changes in the brain can lead to the death of dopamine-synthesizing cells of the substantia nigra and dysfunction of other mediator systems, as well as partial cellular atrophy in the neocortex and subcortical nuclei. As a result, the functioning of neural networks involved in the transmission of information related to the regulation of motor activity and cognitive functions is disrupted. Elucidation of the causes of changes occurring in PD and the search for methods to eliminate them will help create new approaches in the treatment of this disease. The aim of the review is to analyze the pathological processes in the brain that underlie the onset of cognitive impairment in PD. The review analyzes the data obtained both from studies on patients with PD and animal (rodents and primates) models of this disease used for the evaluation of the mechanisms underlying etiology and the development of PD in humans.
Biochemistry. 2023;88(11):2289-2307
2289-2307
The function of the conserved “non-functional” residues in apomyoglobin is to provide and preserve the correct protein topology
Abstract
In this paper the answer to O. B. Ptitsyn’s question “What is the role of conserved non-functional residues in apomyoglobin” is presented, which is based on the research results of three laboratories. The role of conserved non-functional apomyoglobin residues in formation of native topology in the molten globule state of this protein is revealed. This fact allows suggesting that the conserved non-functional residues in this protein are indispensable for fixation and maintaining main elements of the correct topology of its secondary structure in the intermediate state. The correct topology is a native element in the intermediate state of the protein.
Biochemistry. 2023;88(11):2308-2313
2308-2313
Differences in structural changes and pathophysiologic effects of low-density lipoproteins upon accumulation of acylhydroperoxy derivatives in their outer phospholipid monolayer or upon chemical modification of apoprotein b-100 by natural dicarbonyl
Abstract
Nanoparticles of the lipid-transporting system of the organism - low-density lipoproteins (LDL) of blood plasma are easily subjected to free radical peroxidation with formation of their main modified forms - oxidized LDL itself (containing hydroperoxy-acyls in phospholipids of the outer layer of particles) and dicarbonyl-modified LDL (apoprotein B-100 of which was chemically modified by the Maillard reaction). Based on the study of free radical oxidation kinetics of LDL, it was found that the existing in the literature designation “oxidized lipoproteins” is incorrect because it does not reveal the nature of oxidative modification of LDL. It is shown that “atherogenic” LDL (particles of which are actively captured by cultured macrophages) are not the oxidized LDL (in which LOOH-derivatives of phospholipids are formed by enzymatic oxidation of of C-15 lipoxygenase of rabbit reticulocytes), but dicarbonyl-modified LDL. The important role of dicarbonyl-modified LDL in the molecular mechanisms of atherogenesis and endothelial dysfunction is discussed.
Biochemistry. 2023;88(11):2314-2325
2314-2325
Effects of progesterone and selective ligands of membrane progesterone receptors in HepG2 cells of human hepatocellular carcinoma
Abstract
Progesterone exerts multiple effects in different tissues through nuclear receptors (nPRs) and through membrane receptors of the adiponectin and progestin receptor (mPRs) family. The effect of progesterone on cells through different types of receptors can vary significantly. At the same time, it affects the processes of proliferation and apoptosis in normal and tumor tissues in a dual way, stimulating proliferation and carcinogenesis in some tissues, suppressing them and stimulating cell death in others. In this study, we have shown the presence of a high level of mRNA and mPRβ protein in HepG2 tumor cells of human hepatocellular carcinoma. Expression of other membrane and classical nuclear receptors was not detected. May be mPRβ has an important function in HepG2 cells. The main goal of the work was to study the function of this protein and the mechanisms of its action in human hepatocellular carcinoma cells. Previously, we have identified selective mPRs ligands, compounds LS-01 and LS-02, which do not interact with nuclear receptors. Their employment allows differentiating the effects of progestins mediated by different types of receptors. The work studied the effects of progesterone, LS-01 and LS-02 on the proliferation and death of HepG2 cells, as well as the activating phosphorylation of two kinases, p38 MAPK and JNK, under the action of three steroids. It was shown that all three progestins after 72 hours of incubation with cells suppressed their viability and stimulated the appearance of phosphatidylserine on the outer surface of membranes, which was detected by binding to V-FITC annexin, but they did not affect DNA fragmentation of cell nuclei. Progesterone significantly reduced the expression of proliferation marker genes and stimulated the expression of the p21 protein gene, but had a suppressive effect on the expression of some proapoptotic factor genes. All three steroids activated JNK in these cells, but had no effect on p38 MAPK activity. The effects of progesterone and selective mPRs ligands in HepG2 cells were the same in terms of suppression of proliferation and stimulation of apoptotic changes in outer membranes, therefore, they were mediated through interaction with mPRβ. JNK is a member of the signaling cascade activated in these cells by the studied steroids.
Biochemistry. 2023;88(11):2326-2339
2326-2339
Characteristics of PRIMPOL knockout А549 cell response to genоtoxic stress
Abstract
Human DNA primase/polymerase PrimPol synthesizes DNA primers de novo after replication fork stalling at damaged DNA sites, contributing to DNA damage tolerance. The contribution of PrimPol in response to the various types of DNA damage is not fully understood. We obtained the lung carcinoma cells A549 with PRIMPOL knockout and characterized its response to DNA damage caused by hydrogen peroxide, methylmethanesulfonate (MMS), cisplatin, bleomycin and ionizing radiation. Knockout of PRIMPOL reduced the number of proliferating cells and cells in G2 phase after treatment with MMS, caused a more pronounced delay of cisplatin-treated cells in S phase. A significant increase in the proportion of apoptotic cells was noted in PRIMPOL-/- cells in response to ionizing radiation at a dose of 10 Gy, while the proportion of cells prone to necroptosis increased significantly in both parental and knockout cells at any radiation dose. Under conditions of oxidative stress stimulated by hydrogen peroxide, PRIMPOL knockout increased cell viability, measured by the MTT method. The data obtained indicate the involvement of PRIMPOL in modulating stress-adaptive responses to various types of genotoxic stress.
Biochemistry. 2023;88(11):2340-2352
2340-2352