Serine proteases increase oxidative stress in lung cells

2001 ◽  
Vol 281 (3) ◽  
pp. L556-L564 ◽  
Author(s):  
Kazutetsu Aoshiba ◽  
Kimihiko Yasuda ◽  
Shuji Yasui ◽  
Jun Tamaoki ◽  
Atsushi Nagai
Keyword(s):  
Oxidative Stress ◽  
Serine Proteases ◽  
Direct Interaction ◽  
Lung Fibroblasts ◽  
Lung Cells ◽  
Cellular Injury ◽  
Oxygen Species ◽  
Cytotoxic Effects ◽  
Bronchial Epithelial ◽  
High Concentrations

Several serine proteases are directly cytotoxic. We investigated whether the cytotoxic effects of proteases are associated with increased levels of reactive oxygen species (ROS) in cells. We found that treatment of lung fibroblasts or bronchial epithelial cells with relatively high concentrations (0.1–100 U/ml) of neutrophil elastase, trypsin, and Pronase increased ROS levels in the mitochondria and cytoplasm. The protease-induced increase in ROS was associated with oxidative cellular injury as determined by generation of 8-hydroxy-2′-deoxyguanosine and malonaldehyde plus 4-hydroxyalkenal. The protease-induced increase in ROS was not merely due to cell detachment because the proteases also caused an increase in ROS in suspended cells, which precluded attachment to the extracellular matrix. The protease-induced increase in ROS appears to contribute to cytotoxicity because cell death induced by proteases was attenuated by treatment with catalase, a decomposer of H2O2, and accelerated by treatment with aminotriazole, a catalase inhibitor. These results suggest that several proteases increase oxidative stress, indicating a direct interaction between proteases and ROS in mediating cytotoxicity.

scholarly journals Ovothiol A is the Main Antioxidant in Fish Lens

Metabolites ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. 95 ◽  
Author(s):  
Vadim V. Yanshole ◽  
Lyudmila V. Yanshole ◽  
Ekaterina A. Zelentsova ◽  
Yuri P. Tsentalovich
Keyword(s):  
Oxidative Stress ◽  
Freshwater Fish ◽  
Rutilus Rutilus ◽  
Fish Tissue ◽  
Oxygen Species ◽  
Sander Lucioperca ◽  
Marine Animals ◽  
Fiber Cells ◽  
Tissue Protection ◽  
High Concentrations

Tissue protection from oxidative stress by antioxidants is of vital importance for cellular metabolism. The lens mostly consists of fiber cells lacking nuclei and organelles, having minimal metabolic activity; therefore, the defense of the lens tissue from the oxidative stress strongly relies on metabolites. Protein-free extracts from lenses and gills of freshwater fish, Sander lucioperca and Rutilus rutilus lacustris, were subjected to analysis using high-field 1H NMR spectroscopy and HPLC with optical and high-resolution mass spectrometric detection. It was found that the eye lenses of freshwater fish contain high concentrations of ovothiol A (OSH), i.e., one of the most powerful antioxidants exciting in nature. OSH was identified and quantified in millimolar concentrations. The concentration of OSH in the lens and gills depends on the fish genus and on the season. A possible mechanism of the reactive oxygen species deactivation in fish lenses is discussed. This work is the first to report on the presence of OSH in vertebrates. The presence of ovothiol in the fish tissue implies that it may be a significantly more common antioxidant in freshwater and marine animals than was previously thought.

scholarly journals Impacts of Oxidative Stress and Antioxidants on Semen Functions

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Amrit Kaur Bansal ◽  
G. S. Bilaspuri
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Sperm Quality ◽  
Reactive Oxygen ◽  
The Body ◽  
Atp Depletion ◽  
Contributory Factor ◽  
Ros Generation ◽  
Oxygen Species ◽  
High Concentrations

Oxidative stress (OS) has been considered a major contributory factor to the infertility. Oxidative stress is the result of imbalance between the reactive oxygen species (ROS) and antioxidants in the body which can lead to sperm damage, deformity, and eventually male infertility. Although high concentrations of the ROS cause sperm pathology (ATP depletion) leading to insufficient axonemal phosphorylation, lipid peroxidation, and loss of motility and viability but, many evidences demonstrate that low and controlled concentrations of these ROS play an important role in sperm physiological processes such as capacitation, acrosome reaction, and signaling processes to ensure fertilization. The supplementation of a cryopreservation extender with antioxidant has been shown to provide a cryoprotective effect on mammalian sperm quality. This paper reviews the impacts of oxidative stress and reactive oxygen species on spermatozoa functions, causes of ROS generation, and antioxidative strategies to reduce OS. In addition, we also highlight the emerging concept of utilizing OS as a tool of contraception.

Polyamine stimulation perturbs intracellular Ca2+ homeostasis and decreases viability of breast cancer BT474 cells

2020 ◽  
Vol 75 (3-4) ◽  
pp. 65-73
Author(s):  
Louis W.C. Chow ◽  
Kar-Lok Wong ◽  
Lian-Ru Shiao ◽  
King-Chuen Wu ◽  
Yuk-Man Leung
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Er Stress ◽  
Cyclopiazonic Acid ◽  
Oxygen Species ◽  
Reactive Oxygen Species Formation ◽  
Cytotoxic Effects ◽  
Store Depletion ◽  
Species Formation ◽  
Cancer Cell Survival

AbstractIntracellular polyamines such as spermine and spermidine are essential to cell growth in normal and especially in cancer cells. However, whether extracellular polyamines affect cancer cell survival is unknown. We therefore examined the actions of extracellular polyamines on breast cancer BT474 cells. Our data showed that spermine, spermidine, and putrescine decreased cell viability by apoptosis. These polyamines also elicited Ca2+ signals, but the latter were unlikely triggered via Ca2+-sensing receptor (CaSR) as BT474 cells have been demonstrated previously to lack CaSR expression. Spermine-elicited Ca2+ response composed of both Ca2+ release and Ca2+ influx. Spermine caused a complete discharge of the cyclopiazonic acid (CPA)-sensitive Ca2+ pool and, expectedly, endoplasmic reticulum (ER) stress. The Ca2+ influx pore opened by spermine was Mn2+-impermeable, distinct from the CPA-triggered store-operated Ca2+ channel, which was Mn2+-permeable. Spermine cytotoxic effects were not due to oxidative stress, as spermine did not trigger reactive oxygen species formation. Our results therefore suggest that spermine acted on a putative polyamine receptor in BT474 cells, causing cytotoxicity by Ca2+ overload, Ca2+ store depletion, and ER stress.

scholarly journals Effects of Aqueous Dispersions of C60, C70 and Gd@C82 Fullerenes on Genes Involved in Oxidative Stress and Anti-inflammatory Pathways

2021 ◽  
Author(s):  
Elena V. Proskurnina ◽  
Ivan V. Mikheev ◽  
Ekaterina A. Savinova ◽  
Elizaveta S. Ershova ◽  
Natalia N. Veiko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fetal Lung ◽  
Vital Role ◽  
Lung Fibroblasts ◽  
Heme Oxygenase 1 ◽  
Aqueous Dispersions ◽  
Ros Homeostasis ◽  
Intracellular Ros ◽  
Anti Inflammatory ◽  
High Concentrations

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results & conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

scholarly journals Cytotoxic Effects of Coated Gold Nanoparticles on PC12 Cancer Cell

2018 ◽  
Vol 7 ◽  
pp. e1110
Author(s):  
Hadi Zare Marzouni ◽  
Fazel Tarkhan ◽  
Amir Aidun ◽  
Kiana Shahzamani ◽  
Hamid Reza Jahan Tigh ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Amino Acid ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Oxygen Species ◽  
Cytotoxic Effects ◽  
Coated Nanoparticles ◽  
Cellular Life ◽  
Cellular Reactive Oxygen Species ◽  
High Concentrations

Background: The use of gold nanoparticles in medicine and especially in cancer treatment has been of interest to researchers. The effectiveness of this nanoparticle on cells significantly depends on the amount of its entry into the cells. This study was performed to compare the rate and mechanism of effect of gold nanoparticles coated with different amino acid on PC12 cancer cell line.Materials and Methods: The PC12 cells line were exposed to various concentrations of amino acid coated and uncoated gold nanoparticles (0.5, 2.5 and 5 μM). Cell death rate was determined according to level of Lactate dehydrogenase (LDH) release from cells and MTT assay. In addition cell morphology and the amount of Cellular Reactive oxygen species (ROS) were studied.Results: The uncoated gold nanoparticles have shown minor effects on cellular life. Gold nanoparticles coated by tryptophan at high concentrations (2.5, 5 and 25μM) increase in cancer cells metabolic activity. Gold nanoparticles coated by Aspartate also produce the largest amount of LDH and ROS in cancer cells and therefore caused of highest rate of apoptosis.Conclusion: The results showed that the nanoparticles coated with amino acids are affected on cellular metabolism and apoptosis more than uncoated nanoparticles. Also the smallest coated nanoparticles (coated by aspartate) have the most influence and by increasing the size, this effect was reduced. [GMJ.2018;7:e1110]

Reactive oxygen species induce reversible PECAM-1 tyrosine phosphorylation and SHP-2 binding

2003 ◽  
Vol 285 (6) ◽  
pp. H2336-H2344 ◽  
Author(s):  
Matthias Maas ◽  
Ronggang Wang ◽  
Cathy Paddock ◽  
Srigiridhar Kotamraju ◽  
Balaraman Kalyanaraman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Phosphatase ◽  
Reactive Oxygen ◽  
Protein Tyrosine Phosphatases ◽  
Sh2 Domain ◽  
Oxygen Species ◽  
Protein Tyrosine ◽  
High Concentrations

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) functions to control the activation and survival of the cells on which it is expressed. Many of the regulatory functions of PECAM-1 are dependent on its tyrosine phosphorylation and subsequent recruitment of the Src homology (SH2) domain containing protein tyrosine phosphatase SHP-2. The recent demonstration that PECAM-1 tyrosine phosphorylation occurs in cells exposed to the reactive oxygen species hydrogen peroxide (H2O2) suggested that this form of oxidative stress may also support PECAM-1/SHP-2 complex formation. In the present study, we show that PECAM-1 tyrosine phosphorylation in response to exposure of cells to H2O2 is reversible, involves a shift in the balance between kinase and phosphatase activities, and supports binding of SHP-2 and recruitment of this phosphatase to cell-cell borders. We speculate, however, that the unique ability of H2O2 to reversibly oxidize the reactive site cysteine residues of protein tyrosine phosphatases may result in transient inactivation of the SHP-2 that is bound to PECAM-1 under these conditions. Finally, we provide evidence that PECAM-1 tyrosine phosphorylation and SHP-2 binding in endothelial cells requires exposure to an “oxidative burst” of H2O2, but that exposure of these cells to sufficiently high concentrations of H2O2 for a sufficiently long period of time abrogates binding of SHP-2 to tyrosine-phosphorylated PECAM-1. These findings support a role for PECAM-1 as a sensor of oxidative stress, perhaps most importantly during the process of inflammation.

scholarly journals Effects of Aqueous Dispersions of C60, C70 and Gd@C82 Fullerenes on Genes Involved in Oxidative Stress and Anti-Inflammatory Pathways

2021 ◽  
Vol 22 (11) ◽  
pp. 6130
Author(s):  
Elena V. Proskurnina ◽  
Ivan V. Mikheev ◽  
Ekaterina A. Savinova ◽  
Elizaveta S. Ershova ◽  
Natalia N. Veiko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Inflammatory Responses ◽  
Reactive Oxygen ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Heme Oxygenase 1 ◽  
Oxygen Species ◽  
Aqueous Dispersions ◽  
Anti Inflammatory

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory responses are of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 h. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results & conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in reactive oxygen species (ROS) homeostasis. Low and high concentrations of aqueous fullerene dispersions (AFD) have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both “prooxidant” and “antioxidant” effects but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

scholarly journals Cell-specific toxicity of short-term JUUL aerosol exposure to human bronchial epithelial cells and murine macrophages exposed at the air–liquid interface

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Rakeysha Pinkston ◽  
Hasan Zaman ◽  
Ekhtear Hossain ◽  
Arthur L. Penn ◽  
Alexandra Noël
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Cell Lines ◽  
Lung Cells ◽  
Oxygen Species ◽  
Bronchial Epithelial ◽  
Murine Macrophages ◽  
The Us ◽  
Air Liquid Interface

Abstract Backgroud JUUL, an electronic nicotine delivery system (ENDS), which first appeared on the US market in 2015, controled more than 75% of the US ENDS sales in 2018. JUUL-type devices are currently the most commonly used form of ENDS among youth in the US. In contrast to free-base nicotine contained in cigarettes and other ENDS, JUUL contains high levels of nicotine salt (35 or 59 mg/mL), whose cellular and molecular effects on lung cells are largely unknown. In the present study, we evaluated the in vitro toxicity of JUUL crème brûlée-flavored aerosols on 2 types of human bronchial epithelial cell lines (BEAS-2B, H292) and a murine macrophage cell line (RAW 264.7). Methods Human lung epithelial cells and murine macrophages were exposed to JUUL crème brûlée-flavored aerosols at the air–liquid interface (ALI) for 1-h followed by a 24-h recovery period. Membrane integrity, cytotoxicity, extracellular release of nitrogen species and reactive oxygen species, cellular morphology and gene expression were assessed. Results Crème brûlée-flavored aerosol contained elevated concentrations of benzoic acid (86.9 μg/puff), a well-established respiratory irritant. In BEAS-2B cells, crème brûlée-flavored aerosol decreased cell viability (≥ 50%) and increased nitric oxide (NO) production (≥ 30%), as well as iNOS gene expression. Crème brûlée-flavored aerosol did not affect the viability of either H292 cells or RAW macrophages, but increased the production of reactive oxygen species (ROS) by ≥ 20% in both cell types. While crème brûlée-flavored aerosol did not alter NO levels in H292 cells, RAW macrophages exposed to crème brûlée-flavored aerosol displayed decreased NO (≥ 50%) and down-regulation of the iNOS gene, possibly due to increased ROS. Additionally, crème brûlée-flavored aerosol dysregulated the expression of several genes related to biotransformation, inflammation and airway remodeling, including CYP1A1, IL-6, and MMP12 in all 3 cell lines. Conclusion Our results indicate that crème brûlée-flavored aerosol causes cell-specific toxicity to lung cells. This study contributes to providing scientific evidence towards regulation of nicotine salt-based products.

scholarly journals Exposure Effects Beyond the Epithelial Barrier: Transepithelial Induction of Oxidative Stress by Diesel Exhaust Particulates in Lung Fibroblasts in an Organotypic Human Airway Model

2020 ◽  
Vol 177 (1) ◽  
pp. 140-155
Author(s):  
Samantha C Faber ◽  
Nicole A McNabb ◽  
Pablo Ariel ◽  
Emily R Aungst ◽  
Shaun D McCullough
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cell ◽  
Adverse Effects ◽  
Diesel Exhaust ◽  
Bronchial Epithelial Cell ◽  
Human Bronchial Epithelial Cell ◽  
Lung Fibroblasts ◽  
Epithelial Barrier ◽  
Bronchial Epithelial

Abstract In vitro bronchial epithelial monoculture models have been pivotal in defining the adverse effects of inhaled toxicant exposures; however, they are only representative of one cellular compartment and may not accurately reflect the effects of exposures on other cell types. Lung fibroblasts exist immediately beneath the bronchial epithelial barrier and play a central role in lung structure and function, as well as disease development and progression. We tested the hypothesis that in vitro exposure of a human bronchial epithelial cell barrier to the model oxidant diesel exhaust particulates caused transepithelial oxidative stress in the underlying lung fibroblasts using a human bronchial epithelial cell and lung fibroblast coculture model. We observed that diesel exhaust particulates caused transepithelial oxidative stress in underlying lung fibroblasts as indicated by intracellular accumulation of the reactive oxygen species hydrogen peroxide, oxidation of the cellular antioxidant glutathione, activation of NRF2, and induction of oxidative stress-responsive genes. Further, targeted antioxidant treatment of lung fibroblasts partially mitigated the oxidative stress response gene expression in adjacent human bronchial epithelial cells during diesel exhaust particulate exposure. This indicates that exposure-induced oxidative stress in the airway extends beyond the bronchial epithelial barrier and that lung fibroblasts are both a target and a mediator of the adverse effects of inhaled chemical exposures despite being separated from the inhaled material by an epithelial barrier. These findings illustrate the value of coculture models and suggest that transepithelial exposure effects should be considered in inhalation toxicology research and testing.

scholarly journals Intracellular Redox-Balance Involvement in Temozolomide Resistance-Related Molecular Mechanisms in Glioblastoma

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1315 ◽  
Author(s):  
Alessia Lo Dico ◽  
Daniela Salvatore ◽  
Cristina Martelli ◽  
Dario Ronchi ◽  
Cecilia Diceglie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Mechanisms ◽  
Redox Balance ◽  
Oxygen Species ◽  
Cytotoxic Effects ◽  
Mitochondrial Ros ◽  
Resistance Fluctuations ◽  
First Time ◽  
Chaperone Mediated Autophagy

Glioblastoma (GBM) is the most common astrocytic-derived brain tumor in adults, characterized by a poor prognosis mainly due to the resistance to the available therapy. The study of mitochondria-derived oxidative stress, and of the biological events that orbit around it, might help in the comprehension of the molecular mechanisms at the base of GBM responsiveness to Temozolomide (TMZ). Sensitive and resistant GBM cells were used to test the role of mitochondrial ROS release in TMZ-resistance. Chaperone-Mediated Autophagy (CMA) activation in relation to reactive oxygen species (ROS) release has been measured by monitoring the expression of specific genes. Treatments with H2O2 were used to test their potential in reverting resistance. Fluctuations of cytoplasmic ROS levels were accountable for CMA induction and cytotoxic effects observed in TMZ sensitive cells after treatment. On the other hand, in resistant cells, TMZ failed in producing an increase in cytoplasmic ROS levels and CMA activation, preventing GBM cell toxicity. By increasing oxidative stress, CMA activation was recovered, as also cell cytotoxicity, especially in combination with TMZ treatment. Herein, for the first time, it is shown the relation between mitochondrial ROS release, CMA activation and TMZ-responsiveness in GBM.

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