Generation of Reactive Oxygen Species by Quartz Particles and Its Implication for Cellular Damage

ABSTRACT All metazoans produce antimicrobial peptides (AMPs) that have both broad antimicrobial and immunomodulatory activity. Cathelicidins are AMPs that preferentially kill Gram-negative bacteria in vitro, purportedly by assembling into higher-order structures that perforate the membrane. We utilized high-resolution, single-cell fluorescence microscopy to examine their mechanism of action in real time. Engineered cathelicidins rapidly bound to Gram-negative and Gram-positive cells and penetrated the cytoplasmic membrane. Rapid failure of the peptidoglycan superstructure in regions of active turnover caused leakage of cytoplasmic contents and the formation of membrane-bound blebs. A mutation anticipated to destabilize interactions between cathelicidin subunits had no effect on bactericidal activity, suggesting that cathelicidins have activities beyond perforating the membrane. Nanomolar concentrations of cathelicidins, although not bactericidal, reduced the growth rate of Gram-negative and Gram-positive bacteria. The cells exhibited expression changes in multiple essential processes, including protein synthesis, peptidoglycan biosynthesis, respiration, and the detoxification of reactive oxygen species (ROS). Time-lapse imaging revealed that ROS accumulation preceded bleb formation, and treatments that reduced cellular ROS levels overcame these bactericidal effects. We propose that that the primary effect of cathelicidins is to induce the production of ROS that damage bacterial molecules, leading to slowed growth or cell death. Given their low circulating levels in vivo, AMPs may serve to slow bacterial population expansion so that cellular immunity systems can respond to and battle the infection. IMPORTANCE Antimicrobial peptides (AMPs) are an important part of the mammalian innate immune system in the battle against microbial infection. How AMPs function to control bacteria is not clear, as nearly all activity studies use nonphysiological levels of AMPs. We monitored peptide action in live bacterial cells over short time frames with single-cell resolution and found that the primary effect of cathelicidin peptides is to increase the production of oxidative molecules that cause cellular damage in Gram-positive and Gram-negative bacteria.

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The Maillard reaction of a shrimp by-product protein hydrolysate: chemical changes and inhibiting effects of reactive oxygen species in human HepG2 cells

Food & Function ◽

10.1039/c5fo00296f ◽

2015 ◽

Vol 6 (6) ◽

pp. 1919-1927 ◽

Cited By ~ 17

Author(s):

Fengchao Zha ◽

Binbin Wei ◽

Shengjun Chen ◽

Shiyuan Dong ◽

Mingyong Zeng ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Maillard Reaction ◽

Hepg2 Cells ◽

Nutritional Quality ◽

Protein Hydrolysate ◽

Reactive Oxygen ◽

Cellular Damage ◽

Oxygen Species ◽

Chemical Changes

A shrimp by-product protein hydrolysate via the Maillard reaction could alleviate cellular damage, but result in higher HMF and loss of nutritional quality.

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Dystrophic cardiomyopathy: amplification of cellular damage by Ca2+ signalling and reactive oxygen species-generating pathways

Cardiovascular Research ◽

10.1093/cvr/cvm089 ◽

2007 ◽

Vol 77 (4) ◽

pp. 766-773 ◽

Cited By ~ 93

Author(s):

Carole Jung ◽

Adriano S. Martins ◽

Ernst Niggli ◽

Natalia Shirokova

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

Cellular Damage ◽

Oxygen Species ◽

Dystrophic Cardiomyopathy

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Exposure to C. Albicans Makes Bladder Epithelial Cells Induce Apoptosis and Modification of Their Microenvironment

10.21203/rs.3.rs-997243/v1 ◽

2021 ◽

Author(s):

Jayoung Kim ◽

Austin Yeon ◽

Khandakar Tanvir Ahmed ◽

Wei Zhang ◽

Khae-Hawn Kim ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Epithelial Cells ◽

Western Blot ◽

Growth Factor Receptor ◽

Reactive Oxygen ◽

Cellular Damage ◽

Signal Pathways ◽

Oxygen Species ◽

Bladder Pain ◽

Normal Bladder

Abstract INTRODUCTION. Interstitial cystitis/painful bladder syndrome (IC) is characterized by chronic bladder pain and urinary storage symptoms. IC affects more than 3.3 million women in the U.S. alone. Ibis T-5000 assays and next generation sequencing have revealed that the C. albicans fungus is highly abundant in the urine of IC patients, particularly those who report greater pain, urinary urgency, and flares. However, currently, the clinical significance of C. albicans in the urine remains elusive. Here, we report the pathological effects and mechanisms triggered by C. albicans in a healthy normal bladder. METHODS. Immortalized bladder epithelial cells were infected with C. albicans. Perturbations in gene expression were identified using an Affymetrix gene microarray and subsequently followed with bioinformatic analyses, including gene set enrichment. Inflammatory and apoptotic genes were quantified using RT-PCR and Western blot analyses. Central signal pathways were examined using Western blot analysis. RESULTS. DNA microarray analysis showed alterations in the transcriptome of bladder epithelial cells infected with C. albicans over both the short and long terms. Key inflammatory and apoptosis networks were changed, which was consistent with several cellular events. Cellular levels of reactive oxygen species and nitrogen oxide increased after infection. Productions of cyclooxygenase-2 and prostaglandine E2 also increased after C. albicans infection, and their productions were suppressed by blockage of reactive oxygen species-epidermal growth factor receptor-Erk pathway. CONCLUSIONS. This study provides evidence that C. albicans infection triggers inflammation and cellular damage by dysregulating key regulatory genes, signaling pathways, and bioactive species in normal bladder cells.

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Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease

Cells ◽

10.3390/cells9061342 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1342 ◽

Cited By ~ 4

Author(s):

Maria V. Irazabal ◽

Vicente E. Torres

Keyword(s):

Reactive Oxygen Species ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Reactive Oxygen ◽

Public Health Problem ◽

Redox Signaling ◽

Cellular Damage ◽

Antioxidant Systems ◽

Related Factor ◽

Oxygen Species

Chronic kidney disease (CKD) remains a worldwide public health problem associated with serious complications and increased mortality rates. Accumulating evidence indicates that elevated intracellular levels of reactive oxygen species (ROS) play a major role in the pathogenesis of CKD. Increased intracellular levels of ROS can lead to oxidation of lipids, DNA, and proteins, contributing to cellular damage. On the other hand, ROS are also important secondary messengers in cellular signaling. Consequently, normal kidney cell function relies on the “right” amount of ROS. Mitochondria and NADPH oxidases represent major sources of ROS in the kidney, but renal antioxidant systems, such as superoxide dismutase, catalase, or glutathione peroxidase counterbalance ROS-mediated injury. This review discusses the main sources of ROS and antioxidant systems in the kidney, and redox signaling pathways leading to inflammation and fibrosis, which result in abnormal kidney function and CKD progression. We further discuss the important role of the nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating antioxidant responses, and other mechanisms of redox signaling.

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Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification

Journal of Experimental Medicine ◽

10.1084/jem.20062525 ◽

2007 ◽

Vol 204 (7) ◽

pp. 1613-1623 ◽

Cited By ~ 117

Author(s):

Kozo Morita ◽

Takeshi Miyamoto ◽

Nobuyuki Fujita ◽

Yoshiaki Kubota ◽

Keisuke Ito ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Endochondral Ossification ◽

Physiological Role ◽

Reactive Oxygen ◽

Hypertrophic Chondrocytes ◽

Cellular Damage ◽

Oxygen Species ◽

Chondrocyte Hypertrophy ◽

Inhibition Of Proliferation

Chondrocyte hypertrophy during endochondral ossification is a well-controlled process in which proliferating chondrocytes stop proliferating and differentiate into hypertrophic chondrocytes, which then undergo apoptosis. Chondrocyte hypertrophy induces angiogenesis and mineralization. This step is crucial for the longitudinal growth and development of long bones, but what triggers the process is unknown. Reactive oxygen species (ROS) have been implicated in cellular damage; however, the physiological role of ROS in chondrogenesis is not well characterized. We demonstrate that increasing ROS levels induce chondrocyte hypertrophy. Elevated ROS levels are detected in hypertrophic chondrocytes. In vivo and in vitro treatment with N-acetyl cysteine, which enhances endogenous antioxidant levels and protects cells from oxidative stress, inhibits chondrocyte hypertrophy. In ataxia telangiectasia mutated (Atm)–deficient (Atm−/−) mice, ROS levels were elevated in chondrocytes of growth plates, accompanied by a proliferation defect and stimulation of chondrocyte hypertrophy. Decreased proliferation and excessive hypertrophy in Atm−/− mice were also rescued by antioxidant treatment. These findings indicate that ROS levels regulate inhibition of proliferation and modulate initiation of the hypertrophic changes in chondrocytes.

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Mechanism of Microbicidal Action of E-101 Solution, a Myeloperoxidase-Mediated Antimicrobial, and its Oxidative Products

10.1101/394114 ◽

2018 ◽

Author(s):

G. A. Denys ◽

Neil C. Devoe ◽

P. Gudis ◽

M. May ◽

R.C. Allen ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Antimicrobial Activity ◽

Cell Membrane ◽

Whole Blood ◽

Reactive Oxygen ◽

Cellular Damage ◽

Oxygen Species ◽

Protection Assay ◽

Microbicidal Activity ◽

Oxidative Products

ABSTRACTE-101 Solution is a first in class myeloperoxidase-mediated antimicrobial developed for topical application. It is composed of porcine myeloperoxidase (pMPO), glucose oxidase (GO), glucose, sodium chloride, and specific amino acids in an aqueous vehicle. Once activated, the reactive species hydrogen peroxide (H2O2), hypochlorous acid and singlet oxygen are generated. We evaluated the treatment effects of E-101 solution and its oxidative products on ultrastucture changes and microbicidal activity against methicillin-resistantStaphylococcus aureus(MRSA) andEscherichia coli. Time kill and transmission electron microscopy studies were performed using formulations with pMPO or GO omitted. The glutathione membrane protection assay was used to study the neutralization of reactive oxygen species. The potency of E-101 solution was also measured in the presence of serum and whole blood by MIC and MBC determinations. E-101 solution demonstrated rapid bactericidal activity and ultracellular changes in MRSA andE. colicells. When pMPO was omitted, high levels of H2O2generated from GO and glucose demonstrated slow microbicidal activity with minimal cellular damage. When GO was omitted from the formulation no antimicrobial activity or cellular damage was observed. Protection from exposure to E-101 solution reactive oxygen species in the glutathione protection assay was competitive and temporary. E-101 solution maintained its antimicrobial activity in the presence of inhibitory substances such as serum and whole blood. E-101 solution is a potent myeloperoxidase enzyme system with multiple oxidative mechanisms of action. Our findings suggest the primary site that E-101solution exerts microbicidal action is the cell membrane by inactivation of essential cell membrane components.

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Schiff bases of putrescine with methylglyoxal protect from cellular damage caused by accumulation of methylglyoxal and reactive oxygen species in Dictyostelium discoideum

The International Journal of Biochemistry & Cell Biology ◽

10.1016/j.biocel.2017.03.011 ◽

2017 ◽

Vol 86 ◽

pp. 54-66 ◽

Cited By ~ 8

Author(s):

Seong-Jun Park ◽

Min-Kyu Kwak ◽

Sa-Ouk Kang

Keyword(s):

Reactive Oxygen Species ◽

Dictyostelium Discoideum ◽

Schiff Bases ◽

Reactive Oxygen ◽

Cellular Damage ◽

Oxygen Species

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Endothelium-derived reactive oxygen species: their relationship to endothelium-dependent hyperpolarization and vascular tone

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y03-106 ◽

2003 ◽

Vol 81 (11) ◽

pp. 1013-1028 ◽

Cited By ~ 66

Author(s):

Anthie Ellis ◽

Chris R Triggle

Keyword(s):

Reactive Oxygen Species ◽

Hydrogen Peroxide ◽

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Muscle Tone ◽

Reactive Oxygen ◽

Cellular Damage ◽

Oxygen Species ◽

Resistance Arteries ◽

Smooth Muscle Tone

Opinions on the role of reactive oxygen species (ROS) in the vasculature have shifted in recent years, such that they are no longer merely regarded as indicators of cellular damage or byproducts of metabolism they may also be putative mediators of physiological functions. Hydrogen peroxide (H2O2), in particular, can initiate vascular myocyte proliferation (and, incongruously, apoptosis), hyperplasia, cell adhesion, migration, and the regulation of smooth muscle tone. Endothelial cells express enzymes that produce ROS in response to various stimuli, and H2O2 is a potent relaxant of vascular smooth muscle. H2O2 itself can mediate endothelium-dependent relaxations in some vascular beds. Although nitric oxide (NO) is well recognized as an endothelium-derived dilator, it is also well established, particularly in the microvasculature, that another factor, endothelium-derived hyperpolarizing factor (EDHF), is a significant determinant of vasodilatory tone. This review primarily focuses on the hypothesis that H2O2 is an EDHF in resistance arteries. Putative endothelial sources of H2O2 and the effects of H2O2 on potassium channels, calcium homeostasis, and vascular smooth muscle tone are discussed. Furthermore, given the perception that ROS can more likely elicit cytotoxic effects than perform signalling functions, the arguments for and against H2O2 being an endogenous vasodilator are assessed.Key words: reactive oxygen species, hydrogen peroxide (H2O2), endothelium-derived hyperpolarizing factor (EDHF), endothelium, relaxation.

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