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1.
Microorganisms ; 12(4)2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38674676

ABSTRACT

Studies investigating the taxonomic diversity and structure of soil bacteria in areas with enhanced radioactive backgrounds have been ongoing for three decades. An analysis of data published from 1996 to 2024 reveals changes in the taxonomic structure of radioactively contaminated soils compared to the reference, showing that these changes are not exclusively dependent on contamination rates or pollutant compositions. High levels of radioactive exposure from external irradiation and a high radionuclide content lead to a decrease in the alpha diversity of soil bacterial communities, both in laboratory settings and environmental conditions. The effects of low or moderate exposure are not consistently pronounced or unidirectional. Functional differences among taxonomic groups that dominate in contaminated soil indicate a variety of adaptation strategies. Bacteria identified as multiple-stress tolerant; exhibiting tolerance to metals and antibiotics; producing antioxidant enzymes, low-molecular antioxidants, and radioprotectors; participating in redox reactions; and possessing thermophilic characteristics play a significant role. Changes in the taxonomic and functional structure, resulting from increased soil radionuclide content, are influenced by the combined effects of ionizing radiation, the chemical toxicity of radionuclides and co-contaminants, as well as the physical and chemical properties of the soil and the initial bacterial community composition. Currently, the quantification of the differential contributions of these factors based on the existing published studies presents a challenge.

2.
Int J Mol Sci ; 24(24)2023 Dec 10.
Article in English | MEDLINE | ID: mdl-38139144

ABSTRACT

Over the last two decades, a multitude of gain-of-function studies have been conducted on genes that encode antioxidative enzymes, including one of the key enzymes, manganese superoxide dismutase (SOD2). The results of such studies are often contradictory, as they strongly depend on many factors, such as the gene overexpression level. In this study, the effect of altering the ectopic expression level of major transcript variants of the SOD2 gene on the radioresistance of HEK293T cells was investigated using CRISPRa technology. A significant increase in cell viability in comparison with the transfection control was detected in cells with moderate SOD2 overexpression after irradiation at 2 Gy, but not at 3 or 5 Gy. A further increase in the level of SOD2 ectopic expression up to 22.5-fold resulted in increased cell viability detectable only after irradiation at 5 Gy. Furthermore, a 15-20-fold increase in SOD2 expression raised the clonogenic survival of cells after irradiation at 5 Gy. Simultaneous overexpression of genes encoding SOD2 and Catalase (CAT) enhanced clonogenic cell survival after irradiation more effectively than separate overexpression of both. In conjunction with the literature data on the suppression of the procarcinogenic effects of superoxide dismutase overexpression by ectopic expression of CAT, the data presented here suggest the potential efficacy of simultaneous overexpression of SOD2 and CAT to reduce oxidative stress occurring in various pathological processes. Moreover, these results illustrate the importance of selecting the degree of SOD2 overexpression to obtain a protective effect.


Subject(s)
Oxidative Stress , Superoxide Dismutase , Humans , HEK293 Cells , Superoxide Dismutase/metabolism , Transfection
3.
Antioxidants (Basel) ; 11(12)2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36552527

ABSTRACT

Reactive oxygen species (ROS) are normal products of a number of biochemical reactions and are important signaling molecules. However, at the same time, they are toxic to cells and have to be strictly regulated by their antioxidant systems. The etiology and pathogenesis of many diseases are associated with increased ROS levels, and many external stress factors directly or indirectly cause oxidative stress in cells. Within this context, the overexpression of genes encoding the proteins in antioxidant systems seems to have become a viable approach to decrease the oxidative stress caused by pathological conditions and to increase cellular stress resistance. However, such manipulations unavoidably lead to side effects, the most dangerous of which is an increased probability of healthy tissue malignization or increased tumor aggression. The aims of the present review were to collect and systematize the results of studies devoted to the effects resulting from the overexpression of antioxidant system genes on stress resistance and carcinogenesis in vitro and in vivo. In most cases, the overexpression of these genes was shown to increase cell and organism resistances to factors that induce oxidative and genotoxic stress but to also have different effects on cancer initiation and promotion. The last fact greatly limits perspectives of such manipulations in practice. The overexpression of GPX3 and SOD3 encoding secreted proteins seems to be the "safest" among the genes that can increase cell resistance to oxidative stress. High efficiency and safety potential can also be found for SOD2 overexpression in combinations with GPX1 or CAT and for similar combinations that lead to no significant changes in H2O2 levels. Accumulation, systematization, and the integral analysis of data on antioxidant gene overexpression effects can help to develop approaches for practical uses in biomedical and agricultural areas. Additionally, a number of factors such as genetic and functional context, cell and tissue type, differences in the function of transcripts of one and the same gene, regulatory interactions, and additional functions should be taken into account.

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