Antioxidants

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15 pages, 2198 KiB

Open AccessArticle

The Response to Oxidative Damage Correlates with Driver Mutations and Clinical Outcome in Patients with Myelofibrosis

by Elena Genovese, Margherita Mirabile, Sebastiano Rontauroli, Stefano Sartini, Sebastian Fantini, Lara Tavernari, Monica Maccaferri, Paola Guglielmelli, Elisa Bianchi, Sandra Parenti, Chiara Carretta, Selene Mallia, Sara Castellano, Corrado Colasante, Manjola Balliu, Niccolò Bartalucci, Raffaele Palmieri, Tiziana Ottone, Barbara Mora, Leonardo Potenza, Francesco Passamonti, Maria Teresa Voso, Mario Luppi, Alessandro Maria Vannucchi, Enrico Tagliafico, Rossella Manfredini and on behalf of the Mynerva (MYeloid NEoplasms Research Venture AIRC) Show full author list Hide full author list

Antioxidants 2022, 11(1), 113; https://doi.org/10.3390/antiox11010113 - 5 Jan 2022

Cited by 11 | Viewed by 2629

Abstract

Myelofibrosis (MF) is the Philadelphia-negative myeloproliferative neoplasm characterized by the worst prognosis and no response to conventional therapy. Driver mutations in JAK2 and CALR impact on JAK-STAT pathway activation but also on the production of reactive oxygen species (ROS). ROS play a pivotal [...] Read more.

Myelofibrosis (MF) is the Philadelphia-negative myeloproliferative neoplasm characterized by the worst prognosis and no response to conventional therapy. Driver mutations in JAK2 and CALR impact on JAK-STAT pathway activation but also on the production of reactive oxygen species (ROS). ROS play a pivotal role in inflammation-induced oxidative damage to cellular components including DNA, therefore leading to greater genomic instability and promoting cell transformation. In order to unveil the role of driver mutations in oxidative stress, we assessed ROS levels in CD34+ hematopoietic stem/progenitor cells of MF patients. Our results demonstrated that ROS production in CD34+ cells from CALR-mutated MF patients is far greater compared with patients harboring JAK2 mutation, and this leads to increased oxidative DNA damage. Moreover, CALR-mutant cells show less superoxide dismutase (SOD) antioxidant activity than JAK2-mutated ones. Here, we show that high plasma levels of total antioxidant capacity (TAC) correlate with detrimental clinical features, such as high levels of lactate dehydrogenase (LDH) and circulating CD34+ cells. Moreover, in JAK2-mutated patients, high plasma level of TAC is also associated with a poor overall survival (OS), and multivariate analysis demonstrated that high TAC classification is an independent prognostic factor allowing the identification of patients with inferior OS in both DIPSS lowest and highest categories. Altogether, our data suggest that a different capability to respond to oxidative stress can be one of the mechanisms underlying disease progression of myelofibrosis. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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13 pages, 1293 KiB

Open AccessArticle

Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study

by Larissa E. van Eijk, Adriana Tami, Jan-Luuk Hillebrands, Wilfred F. A. den Dunnen, Martin H. de Borst, Peter H. J. van der Voort, Marian L. C. Bulthuis, Alida C. M. Veloo, Karin I. Wold, María F. Vincenti González, Bernardina T. F. van der Gun, Harry van Goor and Arno R. Bourgonje

Antioxidants 2021, 10(12), 2022; https://doi.org/10.3390/antiox10122022 - 20 Dec 2021

Cited by 17 | Viewed by 5464

Abstract

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since [...] Read more.

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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25 pages, 42241 KiB

Open AccessArticle

Radioprotective Role of Vitamins C and E against the Gamma Ray-Induced Damage to the Chemical Structure of Bovine Serum Albumin

by Hajar Zarei, Mostean Bahreinipour, Yahya Sefidbakht, Shokouh Rezaei, Rouhollah Gheisari, Susan Kabudanian Ardestani, Vuk Uskoković and Hiroshi Watabe

Antioxidants 2021, 10(12), 1875; https://doi.org/10.3390/antiox10121875 - 24 Nov 2021

Cited by 5 | Viewed by 2765

Abstract

Radioprotective effects of vitamin C and vitamin E as a water-soluble and a lipid-soluble agent, respectively, were investigated at the molecular level during the imposition of gamma radiation-induced structural changes to bovine serum albumin (BSA) at the therapeutic dose of 3 Gy. Secondary [...] Read more.

Radioprotective effects of vitamin C and vitamin E as a water-soluble and a lipid-soluble agent, respectively, were investigated at the molecular level during the imposition of gamma radiation-induced structural changes to bovine serum albumin (BSA) at the therapeutic dose of 3 Gy. Secondary and tertiary structural changes of control and irradiated BSA samples were investigated using circular dichroism and fluorescence spectroscopy. The preirradiation tests showed nonspecific and reversible binding of vitamins C and E to BSA. Secondary and tertiary structures of irradiated BSA considerably changed in the absence of the vitamins. Upon irradiation, α-helices of BSA transitioned to beta motifs and random coils, and the fluorescence emission intensity decreased relative to nonirradiated BSA. In the presence of the vitamins C or E, however, the irradiated BSA was protected from these structural changes caused by reactive oxygen species (ROS). The two vitamins exhibited different patterns of attachment to the protein surface, as inspected by blind docking, and their mechanisms of protection were different. The hydrophilicity of vitamin C resulted in the predominant scavenging of ROS in the solvent, whereas hydrophobic vitamin E localized on the nonpolar patches of the BSA surface, where it did not only form a barrier for diffusing ROS but also encountered them as an antioxidant and neutralized them thanks to the moderate BSA binding constant. Very low concentrations of vitamins C or E (0.005 mg/mL) appear to be sufficient to prevent the oxidative damage of BSA. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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21 pages, 20604 KiB

Open AccessArticle

Crucial Role of Reactive Oxygen Species (ROS) for the Proapoptotic Effects of Indirubin Derivatives in Cutaneous SCC Cells

by Jiaqi Zhu, Peter Langer, Claas Ulrich and Jürgen Eberle

Antioxidants 2021, 10(10), 1514; https://doi.org/10.3390/antiox10101514 - 24 Sep 2021

Cited by 6 | Viewed by 2323

Abstract

Efficient drugs are needed for countering the worldwide high incidence of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis. Indirubin derivatives represent promising candidates, but their effects in cSCC cells have not been reported before. Here, we investigated the efficacy of three indirubin [...] Read more.

Efficient drugs are needed for countering the worldwide high incidence of cutaneous squamous cell carcinoma (cSCC) and actinic keratosis. Indirubin derivatives represent promising candidates, but their effects in cSCC cells have not been reported before. Here, we investigated the efficacy of three indirubin derivatives (DKP-071, -073 and -184) in four cSCC cell lines. High efficacy was seen in SCL-I, SCL-II, SCC-12 and SCC-13, resulting in up to 80% loss of cell proliferation, 60% loss of cell viability and 30% induced apoptosis (10 µM). Apoptosis was further enhanced in combinations with TNF-related apoptosis-inducing ligand (TRAIL). Induction of reactive oxygen species (ROS) appeared as critical for these effects. Thus, antioxidative pretreatment completely abolished apoptosis as well as restored cell proliferation and viability. Concerning the pathways, complete activation of caspases cascades (caspases-3, -4, -6, -7, -8 and -9), loss of mitochondrial membrane potential, activation of proapoptotic PKCδ (protein kinase C delta), inhibition of STAT3 (signal transducer and activator of transcription 3), downregulation of antiapoptotic XIAP (X-linked inhibitor of apoptosis protein) and survivin as well as upregulation of the proapoptotic Bcl-2 protein Puma and the cell cycle inhibitor p21 were obtained. Importantly, all activation steps were prevented by antioxidants, thus proving ROS as a master regulator of indirubins’ antitumor effects. ROS induction presently develops as an important issue in anticancer therapy. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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34 pages, 5213 KiB

Open AccessArticle

Implications of Oxidative Stress in Glioblastoma Multiforme Following Treatment with Purine Derivatives

by Marta Orlicka-Płocka, Agnieszka Fedoruk-Wyszomirska, Dorota Gurda-Woźna, Paweł Pawelczak, Patrycja Krawczyk, Małgorzata Giel-Pietraszuk, Grzegorz Framski, Tomasz Ostrowski and Eliza Wyszko

Antioxidants 2021, 10(6), 950; https://doi.org/10.3390/antiox10060950 - 12 Jun 2021

Cited by 14 | Viewed by 5538

Abstract

Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status [...] Read more.

Recently, small compound-based therapies have provided new insights into the treatment of glioblastoma multiforme (GBM) by inducing oxidative impairment. Kinetin riboside (KR) and newly designed derivatives (8-azaKR, 7-deazaKR) selectively affect the molecular pathways crucial for cell growth by interfering with the redox status of cancer cells. Thus, these compounds might serve as potential alternatives in the oxidative therapy of GBM. The increased basal levels of reactive oxygen species (ROS) in GBM support the survival of cancer cells and cause drug resistance. The simplest approach to induce cell death is to achieve the redox threshold and circumvent the antioxidant defense mechanisms. Consequently, cells become more sensitive to oxidative stress (OS) caused by exogenous agents. Here, we investigated the effect of KR and its derivatives on the redox status of T98G cells in 2D and 3D cell culture. The use of spheroids of T98G cells enabled the selection of one derivative—7-deazaKR—with comparable antitumor activity to KR. Both compounds induced ROS generation and genotoxic OS, resulting in lipid peroxidation and leading to apoptosis. Taken together, these results demonstrated that KR and 7-deazaKR modulate the cellular redox environment of T98G cells, and vulnerability of these cells is dependent on their antioxidant capacity. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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13 pages, 4540 KiB

Open AccessArticle

Blood Plasma Quality Control by Plasma Glutathione Status

by Tamara Tomin, Natalie Bordag, Elmar Zügner, Abdullah Al-Baghdadi, Maximilian Schinagl, Ruth Birner-Gruenberger and Matthias Schittmayer

Antioxidants 2021, 10(6), 864; https://doi.org/10.3390/antiox10060864 - 27 May 2021

Cited by 7 | Viewed by 4907

Abstract

Timely centrifugation of blood for plasma preparation is a key step to ensure high plasma quality for analytics. Delays during preparation can significantly influence readouts of key clinical parameters. However, in a routine clinical environment, a strictly controlled timeline is often not feasible. [...] Read more.

Timely centrifugation of blood for plasma preparation is a key step to ensure high plasma quality for analytics. Delays during preparation can significantly influence readouts of key clinical parameters. However, in a routine clinical environment, a strictly controlled timeline is often not feasible. The next best approach is to control for sample preparation delays by a marker that provides a readout of the time-dependent degradation of the sample. In this study, we explored the usefulness of glutathione status as potential marker of plasma preparation delay. As the concentration of glutathione in erythrocytes is at least two orders of magnitude higher than in plasma, even the slightest leakage of glutathione from the cells can be readily observed. Over the 3 h observation period employed in this study, we observed a linear increase of plasma concentrations of both reduced (GSH) and oxidized glutathione (GSSG). Artificial oxidation of GSH is prevented by rapid alkylation with N-ethylmaleimide directly in the blood sampling vessel as recently published. The observed relative leakage of GSH was significantly higher than that of GSSG. A direct comparison with plasma lactate dehydrogenase activity, a widely employed hemolysis marker, clearly demonstrated the superiority of our approach for quality control. Moreover, we show that the addition of the thiol alkylating reagent NEM directly to the blood tubes does not influence downstream analysis of other clinical parameters. In conclusion, we report that GSH gives an excellent readout of the duration of plasma preparation and the associated pre-analytical errors. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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15 pages, 5222 KiB

Open AccessArticle

Effects of (–)-Loliolide against Fine Dust Preconditioned Keratinocyte Media-Induced Dermal Fibroblast Inflammation

by Ilekuttige Priyan Shanura Fernando, Mawalle Kankanamge Hasitha Madhawa Dias, Dissanayaka Mudiyanselage Dinesh Madusanka, Hyun-Soo Kim, Eui-Jeong Han, Min-Ju Kim, Min-Jeong Seo and Ginnae Ahn

Antioxidants 2021, 10(5), 675; https://doi.org/10.3390/antiox10050675 - 26 Apr 2021

Cited by 10 | Viewed by 3086

Abstract

At present air pollution in parts of East Asia is at an alarming level due to elevated levels of fine dust (FD). Other than pulmonary complications, FD was found to affect the pathogenesis of ROS-dependent inflammatory responses via penetrating barrier-disrupted skin, leading to [...] Read more.

At present air pollution in parts of East Asia is at an alarming level due to elevated levels of fine dust (FD). Other than pulmonary complications, FD was found to affect the pathogenesis of ROS-dependent inflammatory responses via penetrating barrier-disrupted skin, leading to degradation of extracellular matrix components through the keratinocyte-fibroblast axis. The present study discloses the evaluation of human dermal fibroblast (HDF) responses to FD preconditioned human keratinocyte media (HPM) primed without and with (-)-loliolide (HTT). HPM-FD treatment increased the ROS level in HDFs and activated mitogen-activated protein kinase-derived nuclear factor (NF)-κB inflammatory signaling pathways with a minor reduction of viability. The above events led to cell differentiation and production of matrix metalloproteinases (MMP), increasing collagenase and elastase activity despite the increase of tissue inhibitors of metalloproteinases (TIMP). Media from HTT primed keratinocytes stimulated with FD indicated ameliorated levels of MMPs, inflammatory cytokines, and chemokines in HDFs with suppressed collagenase and elastase activity. Present observations help to understand the factors that affect HDFs in the microenvironment of FD exposed keratinocytes and the therapeutic role of HTT as a suppressor of skin aging. Further studies using organotypic skin culture models could broaden the understanding of the effects of FD and the therapeutic role of HTT. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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18 pages, 8133 KiB

Open AccessArticle

Disruption of Endoplasmic Reticulum and ROS Production in Human Ovarian Cancer by Campesterol

by Hyocheol Bae, Sunwoo Park, Changwon Yang, Gwonhwa Song and Whasun Lim

Antioxidants 2021, 10(3), 379; https://doi.org/10.3390/antiox10030379 - 3 Mar 2021

Cited by 39 | Viewed by 3485

Abstract

Phytosterols, which are present in a variety of foods, exhibit various physiological functions and do not have any side effects. Here, we attempted to identify functional role of campesterol in regulation of oxidative stress by leading to cell death of ovarian cancer. We [...] Read more.

Phytosterols, which are present in a variety of foods, exhibit various physiological functions and do not have any side effects. Here, we attempted to identify functional role of campesterol in regulation of oxidative stress by leading to cell death of ovarian cancer. We investigated the effects of campesterol on cancer cell aggregation using a three-dimensional (3D) culture of human ovarian cancer cells. The effects of campesterol on apoptosis, protein expression, proliferation, the cell cycle, and the migration of these cells were determined to unravel the underlying mechanism. We also investigated whether campesterol regulates mitochondrial function, the generation of reactive oxygen species (ROS), and calcium concentrations. Our results show that campesterol activates cell death signals and cell death in human ovarian cancer cells. Excessive calcium levels and ROS production were induced by campesterol in the two selected ovarian cancer cell lines. Moreover, campesterol suppressed cell proliferation, cell cycle progression, and cell aggregation in ovarian cancer cells. Campesterol also enhanced the anticancer effects of conventional anticancer agents. The present study shows that campesterol can be used as a novel anticancer drug for human ovarian cancer. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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19 pages, 3341 KiB

Open AccessArticle

Extra Virgin Olive Oil Phenolic Extract on Human Hepatic HepG2 and Intestinal Caco-2 Cells: Assessment of the Antioxidant Activity and Intestinal Trans-Epithelial Transport

by Martina Bartolomei, Carlotta Bollati, Maria Bellumori, Lorenzo Cecchi, Ivan Cruz-Chamorro, Guillermo Santos-Sánchez, Giulia Ranaldi, Simonetta Ferruzza, Yula Sambuy, Anna Arnoldi, Nadia Mulinacci and Carmen Lammi

Antioxidants 2021, 10(1), 118; https://doi.org/10.3390/antiox10010118 - 15 Jan 2021

Cited by 14 | Viewed by 4492

Abstract

In the framework of research aimed at promoting the nutraceutical properties of the phenolic extract (BUO) obtained from an extra virgin olive oil of the Frantoio cultivar cultivated in Tuscany (Italy), with a high total phenols content, this study provides a comprehensive characterization [...] Read more.

In the framework of research aimed at promoting the nutraceutical properties of the phenolic extract (BUO) obtained from an extra virgin olive oil of the Frantoio cultivar cultivated in Tuscany (Italy), with a high total phenols content, this study provides a comprehensive characterization of its antioxidant properties, both in vitro by Trolox equivalent antioxidant capacity, oxygen radical absorbance capacity, ferric reducing antioxidant power, and 2,2-diphenyl-1-picrylhydrazyl assays, and at the cellular level in human hepatic HepG2 and human intestinal Caco-2 cells. Notably, in both cell systems, after H₂O₂ induced oxidative stress, the BUO extract reduced reactive oxygen species, lipid peroxidation, and NO overproduction via modulation of inducible nitric oxide synthase protein levels. In parallel, the intestinal transport of the different phenolic components of the BUO phytocomplex was assayed on differentiated Caco-2 cells, a well-established model of mature enterocytes. The novelty of our study lies in having investigated the antioxidant effects of a complex pool of phenolic compounds in an extra virgin olive oil (EVOO) extract, using either in vitro assays or liver and intestinal cell models, rather than the effects of single phenols, such as hydroxytyrosol or oleuropein. Finally, the selective trans-epithelial transport of some oleuropein derivatives was observed for the first time in differentiated Caco-2 cells. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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Review

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18 pages, 1501 KiB

Open AccessReview

Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators—What Are the Consequences

by Philip Newsholme, Jordan Rowlands, Roselyn Rose’Meyer and Vinicius Cruzat

Antioxidants 2022, 11(1), 108; https://doi.org/10.3390/antiox11010108 - 4 Jan 2022

Cited by 6 | Viewed by 4735

Abstract

Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, [...] Read more.

Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, following activation of metabolic pathways such as glycolysis and the TCA cycle. The β-cell cannot protect itself from glucose toxicity by blocking glucose uptake, but indeed relies on alternative metabolic protection mechanisms to avoid dysfunction and death. Alteration of normal metabolic pathway function occurs as a counter regulatory response to high nutrient, inflammatory factor, hormone or therapeutic drug concentrations. Metabolic reprogramming is a term widely used to describe a change in regulation of various metabolic enzymes and transporters, usually associated with cell growth and proliferation and may involve reshaping epigenetic responses, in particular the acetylation and methylation of histone proteins and DNA. Other metabolic modifications such as Malonylation, Succinylation, Hydroxybutyrylation, ADP-ribosylation, and Lactylation, may impact regulatory processes, many of which need to be investigated in detail to contribute to current advances in metabolism. By describing multiple mechanisms of metabolic adaption that are available to the β-cell across its lifespan, we hope to identify sites for metabolic reprogramming mechanisms, most of which are incompletely described or understood. Many of these mechanisms are related to prominent antioxidant responses. Here, we have attempted to describe the key β-cell metabolic adaptions and changes which are required for survival and function in various physiological, pathological and pharmacological conditions. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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15 pages, 660 KiB

Open AccessReview

Reactive Oxygen Species and Pressure Ulcer Formation after Traumatic Injury to Spinal Cord and Brain

by Suneel Kumar, Thomas Theis, Monica Tschang, Vini Nagaraj and Francois Berthiaume

Antioxidants 2021, 10(7), 1013; https://doi.org/10.3390/antiox10071013 - 24 Jun 2021

Cited by 23 | Viewed by 4101

Abstract

Traumatic injuries to the nervous system, including the brain and spinal cord, lead to neurological dysfunction depending upon the severity of the injury. Due to the loss of motor (immobility) and sensory function (lack of sensation), spinal cord injury (SCI) and brain injury [...] Read more.

Traumatic injuries to the nervous system, including the brain and spinal cord, lead to neurological dysfunction depending upon the severity of the injury. Due to the loss of motor (immobility) and sensory function (lack of sensation), spinal cord injury (SCI) and brain injury (TBI) patients may be bed-ridden and immobile for a very long-time. These conditions lead to secondary complications such as bladder/bowel dysfunction, the formation of pressure ulcers (PUs), bacterial infections, etc. PUs are chronic wounds that fail to heal or heal very slowly, may require multiple treatment modalities, and pose a risk to develop further complications, such as sepsis and amputation. This review discusses the role of oxidative stress and reactive oxygen species (ROS) in the formation of PUs in patients with TBI and SCI. Decades of research suggest that ROS may be key players in mediating the formation of PUs. ROS levels are increased due to the accumulation of activated macrophages and neutrophils. Excessive ROS production from these cells overwhelms intrinsic antioxidant mechanisms. While short-term and moderate increases in ROS regulate signal transduction of various bioactive molecules; long-term and excessively elevated ROS can cause secondary tissue damage and further debilitating complications. This review discusses the role of ROS in PU development after SCI and TBI. We also review the completed and ongoing clinical trials in the management of PUs after SCI and TBI using different technologies and treatments, including antioxidants. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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19 pages, 1387 KiB

Open AccessReview

Oxidative Stress as A Mechanism for Functional Alterations in Cardiac Hypertrophy and Heart Failure

by Anureet K. Shah, Sukhwinder K. Bhullar, Vijayan Elimban and Naranjan S. Dhalla

Antioxidants 2021, 10(6), 931; https://doi.org/10.3390/antiox10060931 - 8 Jun 2021

Cited by 91 | Viewed by 5247

Abstract

Although heart failure due to a wide variety of pathological stimuli including myocardial infarction, pressure overload and volume overload is associated with cardiac hypertrophy, the exact reasons for the transition of cardiac hypertrophy to heart failure are not well defined. Since circulating levels [...] Read more.

Although heart failure due to a wide variety of pathological stimuli including myocardial infarction, pressure overload and volume overload is associated with cardiac hypertrophy, the exact reasons for the transition of cardiac hypertrophy to heart failure are not well defined. Since circulating levels of several vasoactive hormones including catecholamines, angiotensin II, and endothelins are elevated under pathological conditions, it has been suggested that these vasoactive hormones may be involved in the development of both cardiac hypertrophy and heart failure. At initial stages of pathological stimuli, these hormones induce an increase in ventricular wall tension by acting through their respective receptor-mediated signal transduction systems and result in the development of cardiac hypertrophy. Some oxyradicals formed at initial stages are also involved in the redox-dependent activation of the hypertrophic process but these are rapidly removed by increased content of antioxidants in hypertrophied heart. In fact, cardiac hypertrophy is considered to be an adaptive process as it exhibits either normal or augmented cardiac function for maintaining cardiovascular homeostasis. However, exposure of a hypertrophied heart to elevated levels of circulating hormones due to pathological stimuli over a prolonged period results in cardiac dysfunction and development of heart failure involving a complex set of mechanisms. It has been demonstrated that different cardiovascular abnormalities such as functional hypoxia, metabolic derangements, uncoupling of mitochondrial electron transport, and inflammation produce oxidative stress in the hypertrophied failing hearts. In addition, oxidation of catecholamines by monoamine oxidase as well as NADPH oxidase activation by angiotensin II and endothelin promote the generation of oxidative stress during the prolonged period by these pathological stimuli. It is noteworthy that oxidative stress is known to activate metallomatrix proteases and degrade the extracellular matrix proteins for the induction of cardiac remodeling and heart dysfunction. Furthermore, oxidative stress has been shown to induce subcellular remodeling and Ca²⁺-handling abnormalities as well as loss of cardiomyocytes due to the development of apoptosis, necrosis, and fibrosis. These observations support the view that a low amount of oxyradical formation for a brief period may activate redox-sensitive mechanisms, which are associated with the development of cardiac hypertrophy. On the other hand, high levels of oxyradicals over a prolonged period may induce oxidative stress and cause Ca²⁺-handling defects as well as protease activation and thus play a critical role in the development of adverse cardiac remodeling and cardiac dysfunction as well as progression of heart failure. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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21 pages, 2548 KiB

Open AccessReview

Effect of Reactive Oxygen Species on the Endoplasmic Reticulum and Mitochondria during Intracellular Pathogen Infection of Mammalian Cells

by Junghwan Lee and Chang-Hwa Song

Antioxidants 2021, 10(6), 872; https://doi.org/10.3390/antiox10060872 - 28 May 2021

Cited by 56 | Viewed by 9236

Abstract

Oxidative stress, particularly reactive oxygen species (ROS), are important for innate immunity against pathogens. ROS directly attack pathogens, regulate and amplify immune signals, induce autophagy and activate inflammation. In addition, production of ROS by pathogens affects the endoplasmic reticulum (ER) and mitochondria, leading [...] Read more.

Oxidative stress, particularly reactive oxygen species (ROS), are important for innate immunity against pathogens. ROS directly attack pathogens, regulate and amplify immune signals, induce autophagy and activate inflammation. In addition, production of ROS by pathogens affects the endoplasmic reticulum (ER) and mitochondria, leading to cell death. However, it is unclear how ROS regulate host defense mechanisms. This review outlines the role of ROS during intracellular pathogen infection, mechanisms of ROS production and regulation of host defense mechanisms by ROS. Finally, the interaction between microbial pathogen-induced ROS and the ER and mitochondria is described. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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39 pages, 3901 KiB

Open AccessEditor’s ChoiceReview

Functions of ROS in Macrophages and Antimicrobial Immunity

by Marc Herb and Michael Schramm

Antioxidants 2021, 10(2), 313; https://doi.org/10.3390/antiox10020313 - 19 Feb 2021

Cited by 316 | Viewed by 32579

Abstract

Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS [...] Read more.

Reactive oxygen species (ROS) are a chemically defined group of reactive molecules derived from molecular oxygen. ROS are involved in a plethora of processes in cells in all domains of life, ranging from bacteria, plants and animals, including humans. The importance of ROS for macrophage-mediated immunity is unquestioned. Their functions comprise direct antimicrobial activity against bacteria and parasites as well as redox-regulation of immune signaling and induction of inflammasome activation. However, only a few studies have performed in-depth ROS analyses and even fewer have identified the precise redox-regulated target molecules. In this review, we will give a brief introduction to ROS and their sources in macrophages, summarize the versatile roles of ROS in direct and indirect antimicrobial immune defense, and provide an overview of commonly used ROS probes, scavengers and inhibitors. Full article

(This article belongs to the Special Issue Reactive Oxygen Species in Different Biological Processes)

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