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Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 13882

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Prof. Dr. Nadezhda S. Kudryasheva

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Institute of Biophysics, Federal Research Center, Siberian Branch of Russian Academy of Sciences, 660041 Krasnoyarsk, Russia
Interests: physicochemistry of biological objects; molecular spectroscopy; structure of molecules; chemiluminescence; bioluminescence; low-dose effects; hormesis; toxicity; radiotoxicity; antioxidant activity; bioactive compounds
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Dear Colleagues,

Low-intensity exposures are the most unexplored field of modern molecular toxicology. A lack of knowledge on the mechanisms of low-intensive factors causes problems in (a) the prediction of biological effects, (b) overcoming negative consequences, and (c) application of positive results. Therefore, the analysis of low impacts is topical from both fundamental and applied standpoints, particularly for ecology, biology, and medicine.

Modern toxicology uses three dose–response models: linear, threshold, and hormesis. The latter implies an activation of physiological functions at low-dose exposures and their inhibition at higher doses and describes these effects in terms of ‘adaptive response’ and ‘toxicity’, respectively. It is supposed that the hormesis model can be applied as a basic one, transforming to the other models under definite restrictions.

Studies of biological responses to bioactive compounds, radiation of different types, etc. under the conditions of low-intensity exposures are encouraged. A chemical and biochemical basis for these responses is of interest.

Prof. Dr. Nadezhda S. Kudryasheva
Guest Editor

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Keywords

low-intensity exposures
bioactive compounds
low-dose radiation
hormesis
toxicity
adaptive response
antioxidant activity
molecular mechanisms
physicochemical processes

Published Papers (7 papers)

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Editorial

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3 pages, 458 KiB

Open AccessEditorial

For Special Issue “Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0” of International Journal of Molecular Sciences

by Nadezhda S. Kudryasheva

Int. J. Mol. Sci. 2023, 24(8), 7665; https://doi.org/10.3390/ijms24087665 - 21 Apr 2023

Viewed by 860

Abstract

The intention of this Special Issue is to highlight the peculiarities of low-intensity/low-concentration exposures for organisms and to examine the molecular mechanisms of the organismal responses [...] Full article

(This article belongs to the Special Issue Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0)

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Research

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23 pages, 2616 KiB

Open AccessArticle

Functionalized Magnetite Nanoparticles: Characterization, Bioeffects, and Role of Reactive Oxygen Species in Unicellular and Enzymatic Systems

by Arina G. Kicheeva, Ekaterina S. Sushko, Lyubov S. Bondarenko, Kamila A. Kydralieva, Denis A. Pankratov, Nataliya S. Tropskaya, Artur A. Dzeranov, Gulzhian I. Dzhardimalieva, Mauro Zarrelli and Nadezhda S. Kudryasheva

Int. J. Mol. Sci. 2023, 24(2), 1133; https://doi.org/10.3390/ijms24021133 - 06 Jan 2023

Cited by 7 | Viewed by 2170

Abstract

The current study evaluates the role of reactive oxygen species (ROS) in bioeffects of magnetite nanoparticles (MNPs), such as bare (Fe₃O₄), humic acids (Fe₃O₄-HA), and 3-aminopropyltriethoxysilane (Fe₃O₄-APTES) modified MNPs. Mössbauer spectroscopy was used to identify the local surrounding for Fe atom/ions and the depth of modification for MNPs. It was found that the Fe₃O₄-HA MNPs contain the smallest, whereas the Fe₃O₄-APTES MNPs contain the largest amount of Fe²⁺ ions. Bioluminescent cellular and enzymatic assays were applied to monitor the toxicity and anti-(pro-)oxidant activity of MNPs. The contents of ROS were determined by a chemiluminescence luminol assay evaluating the correlations with toxicity/anti-(pro-)oxidant coefficients. Toxic effects of modified MNPs were found at higher concentrations (>10⁻² g/L); they were related to ROS storage in bacterial suspensions. MNPs stimulated ROS production by the bacteria in a wide concentration range (10⁻¹⁵–1 g/L). Under the conditions of model oxidative stress and higher concentrations of MNPs (>10⁻⁴ g/L), the bacterial bioassay revealed prooxidant activity of all three MNP types, with corresponding decay of ROS content. Bioluminescence enzymatic assay did not show any sensitivity to MNPs, with negligible change in ROS content. The results clearly indicate that cell-membrane processes are responsible for the bioeffects and bacterial ROS generation, confirming the ferroptosis phenomenon based on iron-initiated cell-membrane lipid peroxidation. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0)

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18 pages, 3318 KiB

Open AccessArticle

Low-Dose-Rate Radiation-Induced Secretion of TGF-β3 Together with an Activator in Small Extracellular Vesicles Modifies Low-Dose Hyper-Radiosensitivity through ALK1 Binding

by Ingunn Hanson, Kathinka E. Pitman, Ursula Altanerova, Čestmír Altaner, Eirik Malinen and Nina F. J. Edin

Int. J. Mol. Sci. 2022, 23(15), 8147; https://doi.org/10.3390/ijms23158147 - 24 Jul 2022

Cited by 4 | Viewed by 1589

Abstract

Hyper-radiosensitivity (HRS) is the increased sensitivity to low doses of ionizing radiation observed in most cell lines. We previously demonstrated that HRS is permanently abolished in cells irradiated at a low dose rate (LDR), in a mechanism dependent on transforming growth factor β3 (TGF-β3). In this study, we aimed to elucidate the activation and receptor binding of TGF-β3 in this mechanism. T-47D cells were pretreated with inhibitors of potential receptors and activators of TGF-β3, along with addition of small extracellular vesicles (sEVs) from LDR primed cells, before their radiosensitivity was assessed by the clonogenic assay. The protein content of sEVs from LDR primed cells was analyzed with mass spectrometry. Our results show that sEVs contain TGF-β3 regardless of priming status, but only sEVs from LDR primed cells remove HRS in reporter cells. Inhibition of the matrix metalloproteinase (MMP) family prevents removal of HRS, suggesting an MMP-dependent activation of TGF-β3 in the LDR primed cells. We demonstrate a functional interaction between TGF-β3 and activin receptor like kinase 1 (ALK1) by showing that TGF-β3 removes HRS through ALK1 binding, independent of ALK5 and TGF-βRII. These results are an important contribution to a more comprehensive understanding of the mechanism behind TGF-β3 mediated removal of HRS. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0)

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21 pages, 14318 KiB

Open AccessArticle

Endohedral Gd-Containing Fullerenol: Toxicity, Antioxidant Activity, and Regulation of Reactive Oxygen Species in Cellular and Enzymatic Systems

by Ekaterina S. Sushko, Natalia G. Vnukova, Grigoriy N. Churilov and Nadezhda S. Kudryasheva

Int. J. Mol. Sci. 2022, 23(9), 5152; https://doi.org/10.3390/ijms23095152 - 05 May 2022

Cited by 9 | Viewed by 1773

Abstract

The Gd-containing metallofullerene derivatives are perspective magnetic resonance imaging contrast agents. We studied the bioeffects of a water-soluble fullerene derivative, gadolinium-endohedral fullerenol, with 40–42 oxygen groups (Gd@Fln). Bioluminescent cellular and enzymatic assays were applied to monitor toxicity and antioxidant activity of Gd@Fln in model solutions; bioluminescence was applied as a signaling physiological parameter. The Gd@Fln inhibited bioluminescence at high concentrations (>2·10⁻¹ gL⁻¹), revealing lower toxicity as compared to the previously studied fullerenols. Efficient activation of bioluminescence (up to almost 100%) and consumption of reactive oxygen species (ROS) in bacterial suspension were observed under low-concentration exposure to Gd@Fln (10⁻³–2·10⁻¹ gL⁻¹). Antioxidant capability of Gd@Fln was studied under conditions of model oxidative stress (i.e., solutions of model organic and inorganic oxidizers); antioxidant coefficients of Gd@Fln were determined at different concentrations and times of exposure. Contents of ROS were evaluated and correlations with toxicity/antioxidant coefficients were determined. The bioeffects of Gd@Fln were explained by hydrophobic interactions, electron affinity, and disturbing of ROS balance in the bioluminescence systems. The results contribute to understanding the molecular mechanism of “hormetic” cellular responses. Advantages of the bioluminescence assays to compare bioeffects of fullerenols based on their structural characteristics were demonstrated. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0)

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20 pages, 3212 KiB

Open AccessArticle

Dose-Dependent Effects of Cold Atmospheric Argon Plasma on the Mesenchymal Stem and Osteosarcoma Cells In Vitro

by Artem M. Ermakov, Olga N. Ermakova, Vera A. Afanasyeva and Anton L. Popov

Int. J. Mol. Sci. 2021, 22(13), 6797; https://doi.org/10.3390/ijms22136797 - 24 Jun 2021

Cited by 14 | Viewed by 2355

Abstract

The antimicrobial, anti-inflammatory and tissue-stimulating effects of cold argon atmospheric plasma (CAAP) accelerate its use in various fields of medicine. Here, we investigated the effects of CAAP at different radiation doses on mesenchymal stem cells (MSCs) and human osteosarcoma (MNNG/HOS) cells. We observed an increase in the growth rate of MSCs at sufficiently low irradiation doses (10–15 min) of CAAP, while the growth of MNNG/HOS cells was slowed down to 41% at the same irradiation doses. Using flow cytometry, we found that these effects are associated with cell cycle arrest and extended death of cancer cells by necrosis. Reactive oxygen species (ROS) formation was detected in both types of cells after 15 min of CAAP treatment. Evaluation of the genes’ transcriptional activity showed that exposure to low doses of CAAP activates the expression of genes responsible for proliferation, DNA replication, and transition between phases of the cell cycle in MSCs. There was a decrease in the transcriptional activity of most of the studied genes in MNNG/HOS osteosarcoma cancer cells. However, increased transcription of osteogenic differentiation genes was observed in normal and cancer cells. The selective effects of low and high doses of CAAP treatment on cancer and normal cells that we found can be considered in terms of hormesis. The low dose of cold argon plasma irradiation stimulated the vital processes in stem cells due to the slight generation of reactive oxygen species. In cancer cells, the same doses evidently lead to the formation of oxidative stress, which was accompanied by a proliferation inhibition and cell death. The differences in the cancer and normal cells’ responses are probably due to different sensitivity to exogenous oxidative stress. Such a selective effect of CAAP action can be used in the combined therapy of oncological diseases such as skin neoplasms, or for the removal of remaining cancer cells after surgical removal of a tumor. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0)

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17 pages, 2316 KiB

Open AccessArticle

Toxicity and Antioxidant Activity of Fullerenol C_60,70 with Low Number of Oxygen Substituents

by Ekaterina S. Kovel, Arina G. Kicheeva, Natalia G. Vnukova, Grigory N. Churilov, Evsei A. Stepin and Nadezhda S. Kudryasheva

Int. J. Mol. Sci. 2021, 22(12), 6382; https://doi.org/10.3390/ijms22126382 - 15 Jun 2021

Cited by 13 | Viewed by 2179

Abstract

Fullerene is a nanosized carbon structure with potential drug delivery applications. We studied the bioeffects of a water-soluble fullerene derivative, fullerenol, with 10-12 oxygen groups (F10-12); its structure was characterized by IR and XPS spectroscopy. A bioluminescent enzyme system was used to study toxic and antioxidant effects of F10-12 at the enzymatic level. Antioxidant characteristics of F10-12 were revealed in model solutions of organic and inorganic oxidizers. Low-concentration activation of bioluminescence was validated statistically in oxidizer solutions. Toxic and antioxidant characteristics of F10-12 were compared to those of homologous fullerenols with a higher number of oxygen groups:F24-28 and F40-42. No simple dependency was found between the toxic/antioxidant characteristics and the number of oxygen groups on the fullerene’s carbon cage. Lower toxicity and higher antioxidant activity of F24-28 were identified and presumptively attributed to its higher solubility. An active role of reactive oxygen species (ROS) in the bioeffects of F10-12 was demonstrated. Correlations between toxic/antioxidant characteristics of F10-12 and ROS content were evaluated. Toxic and antioxidant effects were related to the decrease in ROS content in the enzyme solutions. Our results reveal a complexity of ROS effects in the enzymatic assay system. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0)

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Review

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18 pages, 2536 KiB

Open AccessReview

Marine Bacteria under Low-Intensity Radioactive Exposure: Model Experiments

by Olga V. Kolesnik, Tatiana V. Rozhko and Nadezhda S. Kudryasheva

Int. J. Mol. Sci. 2023, 24(1), 410; https://doi.org/10.3390/ijms24010410 - 27 Dec 2022

Cited by 1 | Viewed by 2009

Abstract

Radioactive contaminants create problems all over world, involving marine ecosystems, with their ecological importance increasing in the future. The review focuses on bioeffects of a series of alpha and beta emitting radioisotopes (americium-241, uranium-(235 + 238), thorium-232, and tritium) and gamma radiation. Low-intensity exposures are under special consideration. Great attention has been paid to luminous marine bacteria as representatives of marine microorganisms and a conventional bioassay system. This bioassay uses bacterial bioluminescence intensity as the main testing physiological parameter; currently, it is widely applied due to its simplicity and sensitivity. Dependences of the bacterial luminescence response on the exposure time and irradiation intensity were reviewed, and applicability of hormetic or threshold models was discussed. A number of aspects of molecular intracellular processes under exposure to low-intensity radiation were analyzed: (a) changes in the rates of enzymatic processes in bacteria with the bioluminescent system of coupled enzymatic reactions of NADH:FMN-oxidoreductase and bacterial luciferase taken as an example; (b) consumption of an intracellular reducer, NADH; (c) active role of reactive oxygen species; (d) repairing of the DNA damage. The results presented confirm the function of humic substances as natural radioprotectors. Full article

(This article belongs to the Special Issue Molecular Mechanisms of Responses to Low-Intensity Exposures 2.0)

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