scholarly journals Sensitivity of Osteosarcoma Cells to Concentration-Dependent Bioactivities of Lipid Peroxidation Product 4-Hydroxynonenal Depend on Their Level of Differentiation

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 269
Author(s):  
Suzana Borovic Sunjic ◽  
Ana Cipak Gasparovic ◽  
Morana Jaganjac ◽  
Gerald Rechberger ◽  
Andreas Meinitzer ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Fatty Acid ◽  
Glutathione Transferase ◽  
Biological Effects ◽  
Protein Adducts ◽  
Transferase Activity ◽  
Lipid Peroxidation Product ◽  
Osteosarcoma Cells ◽  
Proteasomal Activity ◽  
Human Osteosarcoma Cells

4-Hydroxynonenal (HNE) is a major aldehydic product of lipid peroxidation known to exert several biological effects. Normal and malignant cells of the same origin express different sensitivity to HNE. We used human osteosarcoma cells (HOS) in different stages of differentiation in vitro, showing differences in mitosis, DNA synthesis, and alkaline phosphatase (ALP) staining. Differentiated HOS cells showed decreased proliferation (3H-thymidine incorporation), decreased viability (thiazolyl blue tetrazolium bromide-MTT), and increased apoptosis and necrosis (nuclear morphology by staining with 4′,6-diamidino-2-phenylindole-DAPI). Differentiated HOS also had less expressed c-MYC, but the same amount of c-FOS (immunocytochemistry). When exposed to HNE, differentiated HOS produced more reactive oxygen species (ROS) in comparison with undifferentiated HOS. To clarify this, we measured HNE metabolism by an HPLC method, total glutathione (GSH), oxidized GSH (ox GSH), glutathione transferase activity (GST), proteasomal activity by enzymatic methods, HNE-protein adducts by genuine ELISA and fatty acid composition by GC-MS in these cell cultures. Differentiated HOS cells had less GSH, lower HNE metabolism, increased formation of HNE-protein adducts, and lower proteasomal activity, in comparison to undifferentiated counterpart cells, while GST and oxGSH were the same. Fatty acids analyzed by GC-MS showed that there is an increase in C20:3 in differentiated HOS while the amount of C20:4 remained the same. The results showed that the cellular machinery responsible for protection against toxicity of HNE was less efficient in differentiated HOS cells. Moreover, differentiated HOS cells contained more C20:3 fatty acid, which might make them more sensitive to free radical-initiated oxidative chain reactions and more vulnerable to the effects of reactive aldehydes such as HNE. We propose that HNE might act as natural promotor of decay of malignant (osteosarcoma) cells in case of their differentiation associated with alteration of the lipid metabolism.

scholarly journals Cytotoxicity and metabolism of 4-hydroxy-2-nonenal and 2-nonenal in H2O2-resistant cell lines. Do aldehydic by-products of lipid peroxidation contribute to oxidative stress?

1990 ◽  
Vol 267 (2) ◽  
pp. 453-459 ◽  
Author(s):  
D R Spitz ◽  
R R Malcolm ◽  
R J Roberts
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cell Lines ◽  
Glutathione Transferase ◽  
Culture Media ◽  
Chinese Hamster ◽  
Fold Increase ◽  
Fibroblast Cell ◽  
Transferase Activity ◽  
Resistant Cells

Toxic aldehydes, such as 4-hydroxy-2-nonenal (4HNE) and 2-nonenal (2NE), formed during lipid peroxidation have been isolated and implicated in the cytotoxic effects of oxidative stress. We have investigated the cytotoxicity and metabolism of 4HNE and 2NE in control (HA-1) cells and in two H2O2-resistant Chinese hamster fibroblast cell lines. The H2O2-resistant cells were found to be significantly more resistant than HA-1 cells to the cytotoxicity of 4HNE, as determined by clonogenic cell survival (dose-modifying factors at 10% isosurvival of 2.0-3.0). The H2O2-resistant cells demonstrated a significant 2-3-fold increase in the amount of 4HNE removed (mol/cell) from culture media containing 72 microM-4HNE when compared with HA-1 cells. The enhanced ability of H2O2-resistant cells to metabolize 4HNE was abolished by heating the cells at 100 degrees C for 45 min. Similar results were obtained with 2NE. Total glutathione and glutathione transferase activity, believed to be involved in cellular detoxification of 4HNE, were found to be significantly increased (2-3-fold) in the resistant cells when compared with the HA-1 cells. These results show that cell lines adapted and/or selected in a highly peroxidative environment are also resistant to the cytotoxicity of aldehydes formed during lipid peroxidation. This resistance appears to be related to increased cellular metabolism of these aldehydes, possibly through the glutathione transferase system. These findings suggest that the formation of aldehydes due to lipid peroxidation may contribute significantly to the mechanisms of oxidant-induced injury and the selective pressure exerted by H2O2-mediated cytotoxicity in culture.

Aldehydes in Cigarette Smoke React with the Lipid Peroxidation Product Malonaldehyde to Form Fluorescent Protein Adducts on Lysines

2005 ◽  
Vol 18 (5) ◽  
pp. 817-824 ◽  
Author(s):  
Thomas L. Freeman ◽  
Alvin Haver ◽  
Michael J. Duryee ◽  
Dean J. Tuma ◽  
Lynell W. Klassen ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Cigarette Smoke ◽  
Fluorescent Protein ◽  
Protein Adducts ◽  
Lipid Peroxidation Product ◽  
Peroxidation Product

scholarly journals Protective role of L-methionine against free radical damage of rat brain synaptosomes.

2002 ◽  
Vol 49 (4) ◽  
pp. 907-916 ◽  
Author(s):  
Vyacheslav S Slyshenkov ◽  
Anna A Shevalye ◽  
Anton V Liopo ◽  
Lech Wojtczak
Keyword(s):  
Lipid Peroxidation ◽  
Glutathione Reductase ◽  
Rat Brain ◽  
Glutathione Transferase ◽  
Membrane Damage ◽  
Total Content ◽  
Mitochondrial Fraction ◽  
Lipid Peroxidation Product ◽  
Free Radical Damage ◽  
Tert Butylhydroperoxide

Incubation of rat brain synaptosomal/mitochondrial fraction with tert-butylhydroperoxide resulted in accumulation of the lipid peroxidation product, conjugated dienes, damage of the synaptosomal membrane as evidenced by leakage of lactate dehydrogenase, and decrease of the total content of glutathione and of the GSH/GSSG ratio. This treatment also produced a considerable decrease of the ouabain-sensitive ATPase activity and a much smaller diminution of the activities of glutathione reductase and glutathione transferase. Preincubation of the synaptosomal/mitochondrial fraction with 0.5 or 1.0 mM L-methionine significantly protected against lipid peroxidation, membrane damage and changes in the glutathione system produced by low (1 mM) concentrations of tert-butylhydroperoxide and completely prevented inactivation of ouabain-sensitive ATPase, glutathione reductase and glutathione transferase by such treatment. The importance of L-methionine in antioxidant protection is discussed.

scholarly journals Depletion of intracellular glutathione and increased lipid peroxidation mediate cytotoxicity of hematite nanoparticles in MRC-5 cells.

2010 ◽  
Vol 57 (3) ◽  
Author(s):  
Mihaela Radu ◽  
Maria Cristina Munteanu ◽  
Sorina Petrache ◽  
Andreea Iren Serban ◽  
Diana Dinu ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Defense Mechanisms ◽  
Antioxidant Defense ◽  
Glutathione Transferase ◽  
Reduced Glutathione ◽  
Lung Cells ◽  
Lipid Peroxidation Product ◽  
Hematite Nanoparticles ◽  
Mediate Cytotoxicity ◽  
Peroxidation Product

Particles generated from numerous anthropogenic and/or natural sources, such as crystalline α-Fe₂O₃ nanoparticles, have the potential to damage lung cells. In our study we investigated the effects of these nanoparticles (12.5 µg/ml) on lipid peroxidation and the antioxidative system in MRC-5 lung fibroblast cells following exposure for 24, 48 or 72h. Exposure to α-Fe₂O₃ nanoparticles increased lipid peroxidation by 81%, 189% and 110% after 24, 48 and 72h, respectively. Conversely, the reduced glutathione concentration decreased by 23.2% and 51.4% after 48 and 72h of treatment, respectively. In addition, an augmentation of the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase and glutathione reductase within the interval between 48-72h was noticed. Taking into account that the reduced glutathione level decreased and the malondialdehyde level, a lipid peroxidation product, remained highly increased up to 72h of exposure, it would appear that the MRC-5 antioxidant defense mechanisms did not efficiently counteract the oxidative stress induced by exposure to hematite nanoparticles.

scholarly journals The Onset of Systemic Oxidative Stress Associated with the Accumulation of Lipid Peroxidation Product Acrolein in the Skin of Patients with Small-Vessel Vasculitis

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2344
Author(s):  
Vesna Sredoja Tisma ◽  
Stela Bulimbasic ◽  
Danica Galesic Ljubanovic ◽  
Kresimir Galesic ◽  
Jadranka Morovic-Vergles ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Protein Modification ◽  
Protein Adducts ◽  
Small Vessel ◽  
Small Vessel Vasculitis ◽  
Total Serum ◽  
Myeloperoxidase Activity ◽  
Lipid Peroxidation Product ◽  
Systemic Oxidative Stress

Small-vessel vasculitis (SVV) is the inflammation of the vessel wall that can result in hemorrhage and/or ischemia. Among the histological findings in SVV are increased infiltrating neutrophils, which, due to their oxidative burst and myeloperoxidase activity, release excessive reactive oxygen species, triggering a chain reaction of lipid peroxidation and yielding reactive aldehydes such as acrolein. The implication of oxidative stress in the pathogenesis of SVV was studied, focusing on acrolein immunohistochemistry in the affected skin vessels and systemic stress response. Samples from SVV patients and healthy subjects were collected and analyzed for total serum peroxides, total antioxidant capacity, inflammatory and immunological parameters, as well as for the presence of acrolein–protein adducts in the skin tissue specimens. The obtained data showed that systemic redox homeostasis and iron metabolism are altered in SVV patients. Possible biomarkers in the evaluation of oxidative status, disease activity and prevalence were indicated. Furthermore, a strong correlation between the accumulation of acrolein–protein adducts in the skin and the progression of the disease was revealed. Thus, the results of this study demonstrate that SVV is not only associated with systemic oxidative stress but also with tissue-specific oxidative stress that promotes acrolein formation and protein modification correlating with the severity of cutaneous vasculitis.

A comparison of biological effects of modulated carbon-ions and fast neutrons in human osteosarcoma cells

1995 ◽  
Vol 33 (1) ◽  
pp. 135-141 ◽  
Author(s):  
Nobuo Kubota ◽  
Masao Suzuki ◽  
Yoshiya Furusawa ◽  
Koichi Ando ◽  
Sachiko Koike ◽  
...  
Keyword(s):  
Biological Effects ◽  
Fast Neutrons ◽  
Carbon Ions ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

scholarly journals Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1341
Author(s):  
Neven Žarković ◽  
Biserka Orehovec ◽  
Lidija Milković ◽  
Bruno Baršić ◽  
Franz Tatzber ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Inflammatory Diseases ◽  
Protein Adducts ◽  
Lipid Peroxidation Product ◽  
Lethal Outcome ◽  
Dynamic Variations ◽  
Number Of Patients ◽  
Total Antioxidant ◽  
Peroxidation Product ◽  
Sera Samples

Major findings of the pilot study involving 21 critically ill patients during the week after admission to the critical care unit specialized for COVID-19 are presented. Fourteen patients have recovered, while seven passed away. There were no differences between them in respect to clinical or laboratory parameters monitored. However, protein adducts of the lipid peroxidation product 4-hydroxynonenal (HNE) were higher in the plasma of the deceased patients, while total antioxidant capacity was below the detection limit for the majority of sera samples in both groups. Moreover, levels of the HNE-protein adducts were constant in the plasma of the deceased patients, while in survivors, they have shown prominent and dynamic variations, suggesting that survivors had active oxidative stress response mechanisms reacting to COVID-19 aggression, which were not efficient in patients who died. Immunohistochemistry revealed the abundant presence of HNE-protein adducts in the lungs of deceased patients indicating that HNE is associated with the lethal outcome. It seems that HNE was spreading from the blood vessels more than being a consequence of pneumonia. Due to the limitations of the relatively small number of patients involved in this study, further research on HNE and antioxidants is needed. This might allow a better understanding of COVID-19 and options for utilizing antioxidants by personalized, integrative biomedicine approach to prevent the onset of HNE-mediated vitious circle of lipid peroxidation in patients with aggressive inflammatory diseases.

scholarly journals 4-Hydroxy-2-nonenal Induces Apoptosis by Inhibiting AKT Signaling in Human Osteosarcoma Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Guang-rong Ji ◽  
Nai-chun Yu ◽  
Xiang Xue ◽  
Zong-guang Li
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cell Death ◽  
Osteosarcoma Cells ◽  
Physiochemical Properties ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
The Status ◽  
Bodies Of Evidence

The onset of lipid peroxidation within cellular membranes is associated with changes in their physiochemical properties and enzymatic dysfunction of the membrane environment. There are increasing bodies of evidence indicating that aldehydic molecules generated endogenously during the process of lipid peroxidation are causally involved in most of the pathophysiological effects associated with oxidative stress in cells and tissues. 4-Hydroxy-2-nonenal (4-HNE), among them, is believed to be largely responsible for cytopathological effects observed during oxidative stressin vivoand has achieved the status of one of the best recognized and most studied of the cytotoxic products of lipid peroxidation. Here, we reported that 4-HNE treatment may induce cell death in MG63 human osteosarcoma cells. The 4-HNE treatment could activate caspase-3 and alter the Bax/Bcl-2 apoptotic signaling. All these changes are due to the inhibition of AKT activity by 4-HNE treatment, and we also found that the p70S6K activity, downstream factors of AKT, was also blocked by 4-HNE. Our results revealed the molecular mechanism of how 4-HNE induces cell death in MG63 human osteosarcoma cells, which contributes to the clinical treatment of cancer therapy.

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