In living cells Reactive Oxygen Species (ROS) participate in intra- and inter-cellular signaling and all cells contain specific systems that guard redox homeostasis. These systems contain both enzymes which may produce ROS such as NADPH-dependent and other oxidases or nitric oxide synthases, and ROS-neutralizing enzymes such as catalase, peroxiredoxins, thioredoxins, thioredoxin reductases, glutathione reductases, and many others. Most of the genes coding for these enzymes contain sequences targeted by micro RNAs (miRNAs), which are components of RNA-induced silencing complexes and play important roles in inhibiting translation of their targeted messenger RNAs (mRNAs). In this review we describe miRNAs that directly target and can influence enzymes responsible for scavenging of ROS and their possible role in cellular redox homeostasis. Regulation of antioxidant enzymes aims to adjust cells to survive in unstable oxidative environments; however, sometimes seemingly paradoxical phenomena appear where oxidative stress induces an increase in the levels of miRNAs which target genes which are supposed to neutralize ROS and therefore would be expected to decrease antioxidant levels. Here we show examples of such cellular behaviors and discuss the possible roles of miRNAs in redox regulatory circuits and further cell responses to stress.
Ultraviolet A (UVA) radiation is harmful for living organisms but in low doses may stimulate cell proliferation. Our aim was to examine the relationships between exposure to different low UVA doses, cellular proliferation, and changes in cellular reactive oxygen species levels. In human colon cancer (HCT116) and melanoma (Me45) cells exposed to UVA doses comparable to environmental, the highest doses (30–50 kJ/m2) reduced clonogenic potential but some lower doses (1 and 10 kJ/m2) induced proliferation. This effect was cell type and dose specific. In both cell lines the levels of reactive oxygen species and nitric oxide fluctuated with dynamics which were influenced differently by UVA; in Me45 cells decreased proliferation accompanied the changes in the dynamics of H2O2 while in HCT116 cells those of superoxide. Genes coding for proteins engaged in redox systems were expressed differently in each cell line; transcripts for thioredoxin, peroxiredoxin and glutathione peroxidase showed higher expression in HCT116 cells whereas those for glutathione transferases and copper chaperone were more abundant in Me45 cells. We conclude that these two cell types utilize different pathways for regulating their redox status. Many mechanisms engaged in maintaining cellular redox balance have been described. Here we show that the different cellular responses to a stimulus such as a specific dose of UVA may be consequences of the use of different redox control pathways. Assays of superoxide and hydrogen peroxide level changes after exposure to UVA may clarify mechanisms of cellular redox regulation and help in understanding responses to stressing factors.
Superoxide radicals, together with nitric oxide (NO), determine the oxidative status of cells, which use different pathways to control their levels in response to stressing conditions. Using gene expression data available in the Cancer Cell Line Encyclopedia and microarray results, we compared the expression of genes engaged in pathways controlling reactive oxygen species and NO production, neutralization, and changes in response to the exposure of cells to ionizing radiation (IR) in human cancer cell lines originating from different tissues. The expression of NADPH oxidases and NO synthases that participate in superoxide radical and NO production was low in all cell types. Superoxide dismutase, glutathione peroxidase, thioredoxin, and peroxiredoxins participating in radical neutralization showed high expression in nearly all cell types. Some enzymes that may indirectly influence superoxide radical and NO levels showed tissue-specific expression and differences in response to IR. Using fluorescence microscopy and specific dyes, we followed the levels and the distribution of superoxide and NO radicals in living melanoma cells at different times after exposure to IR. Directly after irradiation, we observed an increase of superoxide radicals and NO coexistent in the same subcellular locations, suggesting a switch of NO synthase to the production of superoxide radicals.
21Ultraviolet A (UVA) radiation is harmful for living organisms but in low doses may 22 stimulate cell proliferation. Our aim was to examine the relationships between exposure 23 to different low UVA doses, cellular proliferation, and changes in cellular reactive 24 oxygen species levels. In human colon cancer (HCT116) and melanoma (Me45) cells 25 exposed to UVA doses comparable to environmental, the highest doses (30-50 kJ/m 2 ) 26 reduced clonogenic potential but some lower doses (1 and 10 kJ/m 2 ) induced 27 proliferation. This effect was cell type and dose specific. In both cell lines the levels of 28 reactive oxygen species and nitric oxide fluctuated with dynamics which were 29 influenced differently by UVA; in Me45 cells decreased proliferation accompanied the 30 changes in the dynamics of H 2 O 2 while in HCT116 cells those of superoxide. Genes 31 coding for proteins engaged in redox systems were expressed differently in each cell 32 line; transcripts for thioredoxin, peroxiredoxin and glutathione peroxidase showed 33 higher expression in HCT116 cells whereas those for glutathione transferases and 34 copper chaperone were more abundant in Me45 cells. We conclude that these two cell 35 types utilize different pathways for regulating their redox status. Many mechanisms 36 engaged in maintaining cellular redox balance have been described. Here we show that 37 the different cellular responses to a stimulus such as a specific dose of UVA may be 38 consequences of the use of different redox control pathways. Assays of superoxide and 39 hydrogen peroxide level changes after exposure to UVA may clarify mechanisms of 40 cellular redox regulation and help in understanding responses to stressing factors. 41 42 43 44 Ciesielska 3 45 46 48with a wavelength of 100-400 nm, invisible to human sight. The sun is a natural emitter 49 of UV divided into three main fractions UVA (315-400 nm), UVB (280-315 nm), and 50 UVC (100-280 nm), but most of this radiation is blocked by the atmosphere (1,2). UVA 51 constitutes the largest part (∼95%) of UV radiation that reaches the Earth's surface (3), 52whereas UVB represents only 4-5% (1). In irradiated humans UVA reaches the dermis 53 and hypodermis and has no direct impact on DNA, but it can influence cellular 54 structures indirectly by induction of reactive oxygen species (ROS) which can damage 55 macromolecules (4,1). For a long time UV was regarded as damaging for cells and 56 organisms (5), but since a few decades it is known that low doses can also stimulate 57 proliferation of cells; however, the mechanisms underlying this phenomenon are not 58 completely understood (3,1,6,7). 59Studies of signaling pathways in conditions where UVA stimulates cell proliferation 60 show changes in the levels of proteins engaged in controlling proliferation such as 61 cyclin D1 (8,9), Pin1 (3), and Kin17 (10) or activation of epidermal growth factor 62 receptor (EGFR) which is strongly mitogenic in many cell types (8). Experiments on 63 mice showed that UVA can accelerate tumor growth ...
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