Differences in Structural Changes and Pathophysiological Effects of Low-Density Lipoprotein Particles upon Accumulation of Acylhydroperoxy Derivatives in Their Outer Phospholipid Monolayer or upon Modification of Apoprotein B-100 by Natural Dicarbonyls
AbstractNanoparticles of the lipid-transporting system of the organism, low-density lipoproteins  (LDL) of blood plasma, are prone 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 in which chemically modified via the Mail lard reaction). Based on the study of free radical oxidation kinetics of LDLs, it was found that the existing in the literature designation of “oxidized lipoproteins” is incorrect because it does not reveal the nature of oxidati...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Biochemical and Ultrastructural Changes in Wheat Plants during Drought Stress
We examined four local bread wheat cultivars with different drought tolerance (drought-tolerant Zirva  85 and Murov 2 and drought-sensitive Aran and Gyzyl bughda cultivars). Leaves from seedlings of drought-tolerant plants demonstrated higher activity of antioxidant enzymes and lower levels of malondialdehyde and hydrogen peroxide. The content of soluble proteins in drought-exposed increased, poss ibly due to the stress-induced activation of gene expression and protein synthesis. Drought-exposed Zirva 85 plants exhibited an elevated activity of nitrogen and carbon metabolism enzymes. Ultrastructural analysis by transmis...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Methods for Assessment of Nucleotide Excision Repair Efficiency
AbstractNucleotide excision repair (NER) is responsible for removing a wide variety of bulky adducts from DNA, thus contributing to the maintenance of genome stability. The efficiency with which proteins of the NER system recognize and remove bulky adducts depends on many factors and is of great clinical and diagnostic significance. The review examines current concepts of the NER system molecular basis in eukaryotic cells and analyzes methods for the assessment of the NER-mediated DNA repair efficiency bothin  vitro andex  vivo. (Source: Biochemistry (Moscow))
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Function of the Conserved Non-Functional Residues in Apomyoglobin – to Determine and to Preserve Correct Topology of the Protein
AbstractIn 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 elemen...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Response of PRIMPOL-Knockout Human Lung Adenocarcinoma A549 Cells to Genotoxic Stress
AbstractHuman DNA primase/polymerase PrimPol synthesizes DNA primersde  novo after replication fork stalling at the sites of DNA damage, thus contributing to the DNA damage tolerance. The role of PrimPol in response to the different types of DNA damage is poorly understood. We knocked out thePRIMPOL gene in the lung carcinoma A549 cell line and characterized the response of the obtained cells to the DNA damage caused by hydrogen peroxide, methyl methanesulfonate (MMS), cisplatin, bleomycin, and ionizing radiation. ThePRIMPOL knockout reduced the number of proliferating cells and cells in the G2 phase after treatment with ...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Retrotransposons and Telomeres
AbstractTransposable 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...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Diversity and Evolution of Mitochondrial Translation Apparatus
AbstractThe evolution of mitochondria has proceeded independently in different eukaryotic lines, which is reflected in the diversity of mitochondrial genomes and mechanisms of their expression in eukaryotic species. Mitochondria have lost most of bacterial ancestor genes by transferring them to the nucleus or eliminating them. However, mitochondria of almost all eukaryotic cells still retain relatively small genomes, as well as their replication, transcription, and translation apparatuses. The dependence on the nuclear genome, specific features of mitochondrial transcripts, and synthesis of highly hydrophobic membrane prot...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Pathological Correlates of Cognitive Decline in Parkinson ’s Disease: From Molecules to Neural Networks
AbstractParkinson ’s disease (PD) is a progressive neurodegenerative disorder caused by the death of dopaminergic neurons in the substantia nigra and appearance of protein aggregates (Lewy bodies) consisting predominantly of α-synuclein in neurons. PD is currently recognized as a multisystem disorder characterized by severe motor impairments and various non-motor symptoms. Cognitive decline is one of the most common and worrisome non-motor symptoms. Moderate cognitive impairments (CI) are diagnosed already at the early stages of PD, usually transform into dementia. The main types of CI in PD include executi ve dysfunct...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

To Be Mobile or Not: The Variety of Reverse Transcriptases and Their Recruitment by Host Genomes
AbstractReverse 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 origina...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Effects of Progesterone and Selective Ligands of Membrane Progesterone Receptors in HepG2 Cells of Human Hepatocellular Carcinoma
In this study, we have shown the presence of high level of mPRβ mRNA and protein in the HepG2 cells of human hepatocellular carcinoma. Expression of other membrane and classical nuclear receptors was not det ected. It could imply that mPRβ has an important function in the HepG2 cells. The main goal of the work was to study functions of this protein and mechanisms of its action in human hepatocellular carcinoma cells. Previously, we have identified selective mPRs ligands, compounds LS-01 and LS-02, whic h do not interact with nuclear receptors. Their employment allows differentiating the effects of progestins mediated by ...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

“If I Were in Nature’s Place, I Would Do It Like This...” Life and Hypotheses of Alexey Olovnikov
AbstractIn 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 t...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Potential Geroprotectors – From Bench to Clinic
AbstractGeroprotectors are substances that slow down aging process and can be used for prevention of age-related diseases. Geroprotectors can improve 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 their action on the aging processes. Geroprotectors are required 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 to different targets and mec...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Actuarial Aging Rates in Human 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 coun...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

A Solitary Stalled 80S Ribosome Prevents mRNA Recruitment to Stress Granules
In this study, we evaluated the ability of various small-molecule translation inhibitors to block or stimulate the assembly of SGs under conditions of s evere oxidative stress induced by sodium arsenite. Contrary to expectations, we found that ribosome-targeting elongation inhibitors of a specific type, which arrest solitary 80S ribosomes at the beginning of the mRNA coding regions but do not interfere with all subsequent ribosomes in completing tra nslation and leaving the transcripts (such as harringtonine, lactimidomycin, or T-2 toxin), completely prevent the formation of arsenite-induced SGs. These observations suggest...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research

Immune Privileges as a Result of Mutual Regulation of Immune and Stem Systems
AbstractImmune privileges of cancer stem cells is a well-known and widely studied problem, as presence of such cells in tumors is associated with refractoriness, recurrence, and metastasis. Accumulating evidence also suggests presence of immune privileges in non-pathological stem cells in addition to their other defense mechanisms against damaging factors. This similarity between pathological and normal stem cells raises the question of why stem cells have such a potentially dangerous property. Regulation of vital processes of autoimmunity control and regeneration realized through interactions between immune cells, stem ce...
Source: Biochemistry (Moscow) - November 1, 2023 Category: Biochemistry Source Type: research