Cells

Editorial

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5 pages, 195 KiB

Open AccessEditorial

Roles and Functions of ROS and RNS in Cellular Physiology and Pathology

by Neven Zarkovic

Cells 2020, 9(3), 767; https://doi.org/10.3390/cells9030767 - 21 Mar 2020

Cited by 83 | Viewed by 7154

Abstract

Our common knowledge on oxidative stress has evolved substantially over the years, being focused mostly on the fundamental chemical reactions and the most relevant chemical species involved in human pathophysiology of oxidative stress-associated diseases. Thus, reactive oxygen species and reactive nitrogen species (ROS [...] Read more.

Our common knowledge on oxidative stress has evolved substantially over the years, being focused mostly on the fundamental chemical reactions and the most relevant chemical species involved in human pathophysiology of oxidative stress-associated diseases. Thus, reactive oxygen species and reactive nitrogen species (ROS and RNS) were identified as key players in initiating, mediating, and regulating the cellular and biochemical complexity of oxidative stress either as physiological (acting pro-hormetic) or as pathogenic (causing destructive vicious circles) processes. The papers published in this particular Special Issue of Cells show an impressive range on the pathophysiological relevance of ROS and RNS, including the relevance of second messengers of free radicals like 4-hydroxynonenal, allowing us to assume that the future will reveal even more detailed mechanisms of their positive and negative effects that might improve the monitoring of major modern diseases, and aid the development of advanced integrative biomedical treatments. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

Research

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13 pages, 4076 KiB

Open AccessArticle

Differential Sensitivity of Two Endothelial Cell Lines to Hydrogen Peroxide Toxicity: Relevance for In Vitro Studies of the Blood–Brain Barrier

by Olufemi Alamu, Mariam Rado, Okobi Ekpo and David Fisher

Cells 2020, 9(2), 403; https://doi.org/10.3390/cells9020403 - 10 Feb 2020

Cited by 13 | Viewed by 4656

Abstract

Oxidative stress (OS) has been linked to blood–brain barrier (BBB) dysfunction which in turn has been implicated in the initiation and propagation of some neurological diseases. In this study, we profiled, for the first time, two endothelioma cell lines of mouse brain origin, [...] Read more.

Oxidative stress (OS) has been linked to blood–brain barrier (BBB) dysfunction which in turn has been implicated in the initiation and propagation of some neurological diseases. In this study, we profiled, for the first time, two endothelioma cell lines of mouse brain origin, commonly used as in vitro models of the blood–brain barrier, for their resistance against oxidative stress using viability measures and glutathione contents as markers. OS was induced by exposing cultured cells to varying concentrations of hydrogen peroxide and fluorescence microscopy/spectrometry was used to detect and estimate cellular glutathione contents. A colorimetric viability assay was used to determine changes in the viability of OS-exposed cells. Both the b.End5 and bEnd.3 cell lines investigated showed demonstrable content of glutathione with a statistically insignificant difference in glutathione quantity per unit cell, but with a statistically significant higher capacity for the b.End5 cell line for de novo glutathione synthesis. Furthermore, the b.End5 cells demonstrated greater oxidant buffering capacity to higher concentrations of hydrogen peroxide than the bEnd.3 cells. We concluded that mouse brain endothelial cells, derived from different types of cell lines, differ enormously in their antioxidant characteristics. We hereby recommend caution in making comparisons across BBB models utilizing distinctly different cell lines and require further prerequisites to ensure that in vitro BBB models involving these cell lines are reliable and reproducible. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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19 pages, 2969 KiB

Open AccessArticle

The Charcot–Marie Tooth Disease Mutation R94Q in MFN2 Decreases ATP Production but Increases Mitochondrial Respiration under Conditions of Mild Oxidative Stress

by Christina Wolf, Rahel Zimmermann, Osamah Thaher, Diones Bueno, Verena Wüllner, Michael K.E. Schäfer, Philipp Albrecht and Axel Methner

Cells 2019, 8(10), 1289; https://doi.org/10.3390/cells8101289 - 21 Oct 2019

Cited by 16 | Viewed by 4834

Abstract

Charcot–Marie tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which [...] Read more.

Charcot–Marie tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic, and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented mitochondria but a similar mitochondrial oxygen consumption, membrane potential, and ATP production as wildtype cells. However, when inducing mild oxidative stress 24 h before analysis using 100 µM hydrogen peroxide, R94Q cells exhibited significantly increased respiration but decreased mitochondrial ATP production. This was accompanied by increased glucose uptake and an up-regulation of hexokinase 1 and pyruvate kinase M2, suggesting increased pyruvate shuttling into mitochondria. Interestingly, these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells. We conclude that mitochondria harboring the disease-causing R94Q mutation in MFN2 are more susceptible to oxidative stress, which causes uncoupling of respiration and ATP production possibly by a less efficient mitochondrial quality control. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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28 pages, 4749 KiB

Open AccessFeature PaperArticle

Nutritional Stress in Head and Neck Cancer Originating Cell Lines: The Sensitivity of the NRF2-NQO1 Axis

by Lidija Milković, Marko Tomljanović, Ana Čipak Gašparović, Renata Novak Kujundžić, Dina Šimunić, Paško Konjevoda, Anamarija Mojzeš, Nikola Đaković, Neven Žarković and Koraljka Gall Trošelj

Cells 2019, 8(9), 1001; https://doi.org/10.3390/cells8091001 - 29 Aug 2019

Cited by 17 | Viewed by 5766

Abstract

Nutritional stress disturbs the cellular redox-status, which is characterized by the increased generation of reactive oxygen species (ROS). The NRF2-NQO1 axis represents a protective mechanism against ROS. Its strength is cell type-specific. FaDu, Cal 27 and Detroit 562 cells differ with respect to [...] Read more.

Nutritional stress disturbs the cellular redox-status, which is characterized by the increased generation of reactive oxygen species (ROS). The NRF2-NQO1 axis represents a protective mechanism against ROS. Its strength is cell type-specific. FaDu, Cal 27 and Detroit 562 cells differ with respect to basal NQO1 activity. These cells were grown for 48 hours in nutritional conditions (NC): (a) Low glucose–NC2, (b) no glucose, no glutamine–NC3, (c) no glucose with glutamine–NC4. After determining the viability, proliferation and ROS generation, NC2 and NC3 were chosen for further exploration. These conditions were also applied to IMR-90 fibroblasts. The transcripts/transcript variants of NRF2 and NQO1 were quantified and transcript variants were characterized. The proteins (NRF2, NQO1 and TP53) were analyzed by a western blot in both cellular fractions. Under NC2, the NRF2-NQO1 axis did not appear activated in the cancer cell lines. Under NC3, the NRF2-NQO1axis appeared slightly activated in Detroit 562. There are opposite trends with respect to TP53 nuclear signal when comparing Cal 27 and Detroit 562 to FaDu, under NC2 and NC3. The strong activation of the NRF2-NQO1 axis in IMR-90 resulted in an increased expression of catalytically deficient NQO1, due to NQO1*2/*2 polymorphism (rs1800566). The presented results call for a comprehensive exploration of the stress response in complex biological systems. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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18 pages, 3322 KiB

Open AccessArticle

Cannabidiol Regulates the Expression of Keratinocyte Proteins Involved in the Inflammation Process through Transcriptional Regulation

by Anna Jastrząb, Agnieszka Gęgotek and Elżbieta Skrzydlewska

Cells 2019, 8(8), 827; https://doi.org/10.3390/cells8080827 - 3 Aug 2019

Cited by 93 | Viewed by 10441

Abstract

Cannabidiol (CBD), a natural phytocannabinoid without psychoactive effect, is a well-known anti-inflammatory and antioxidant compound. The possibility of its use in cytoprotection of cells from harmful factors, including ultraviolet (UV) radiation, is an area of ongoing investigation. Therefore, the aim of this study [...] Read more.

Cannabidiol (CBD), a natural phytocannabinoid without psychoactive effect, is a well-known anti-inflammatory and antioxidant compound. The possibility of its use in cytoprotection of cells from harmful factors, including ultraviolet (UV) radiation, is an area of ongoing investigation. Therefore, the aim of this study was to evaluate the effect of CBD on the regulatory mechanisms associated with the redox balance and inflammation in keratinocytes irradiated with UVA [30 J/cm²] and UVB [60 mJ/cm²]. Spectrophotometric results show that CBD significantly enhances the activity of antioxidant enzymes such as superoxide dismutase and thioredoxin reductase in UV irradiated keratinocytes. Furthermore, despite decreased glutathione peroxidase and reductase activities, CBD prevents lipid peroxidation, which was observed as a decreased level of 4-HNE and 15d-PGJ₂ (measured using GC/MS and LC/MS). Moreover, Western blot analysis of protein levels shows that, under stress conditions, CBD influences interactions of transcription factors Nrf2- NFκB by inhibiting the NFκB pathway, increasing the expression of Nrf2 activators and stimulating the transcription activity of Nrf2. In conclusion, the antioxidant activity of CBD through Nrf2 activation as well as its anti-inflammatory properties as an inhibitor of NFκB should be considered during design of new protective treatments for the skin. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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16 pages, 3015 KiB

Open AccessArticle

Intermittent Hypoxia Prevents Myocardial Mitochondrial Ca²⁺ Overload and Cell Death during Ischemia/Reperfusion: The Role of Reactive Oxygen Species

by Jui-Chih Chang, Chih-Feng Lien, Wen-Sen Lee, Huai-Ren Chang, Yu-Cheng Hsu, Yu-Po Luo, Jing-Ren Jeng, Jen-Che Hsieh and Kun-Ta Yang

Cells 2019, 8(6), 564; https://doi.org/10.3390/cells8060564 - 9 Jun 2019

Cited by 62 | Viewed by 6671

Abstract

It has been documented that reactive oxygen species (ROS) contribute to oxidative stress, leading to diseases such as ischemic heart disease. Recently, increasing evidence has indicated that short-term intermittent hypoxia (IH), similar to ischemia preconditioning, could yield cardioprotection. However, the underlying mechanism for [...] Read more.

It has been documented that reactive oxygen species (ROS) contribute to oxidative stress, leading to diseases such as ischemic heart disease. Recently, increasing evidence has indicated that short-term intermittent hypoxia (IH), similar to ischemia preconditioning, could yield cardioprotection. However, the underlying mechanism for the IH-induced cardioprotective effect remains unclear. The aim of this study was to determine whether IH exposure can enhance antioxidant capacity, which contributes to cardioprotection against oxidative stress and ischemia/reperfusion (I/R) injury in cardiomyocytes. Primary rat neonatal cardiomyocytes were cultured in IH condition with an oscillating O₂ concentration between 20% and 5% every 30 min. An MTT assay was conducted to examine the cell viability. Annexin V-FITC and SYTOX green fluorescent intensity and caspase 3 activity were detected to analyze the cell death. Fluorescent images for DCFDA, Fura-2, Rhod-2, and TMRM were acquired to analyze the ROS, cytosol Ca²⁺, mitochondrial Ca²⁺, and mitochondrial membrane potential, respectively. RT-PCR, immunocytofluorescence staining, and antioxidant activity assay were conducted to detect the expression of antioxidant enzymes. Our results show that IH induced slight increases of O₂⁻^· and protected cardiomyocytes against H₂O₂- and I/R-induced cell death. Moreover, H₂O₂-induced Ca²⁺ imbalance and mitochondrial membrane depolarization were attenuated by IH, which also reduced the I/R-induced Ca²⁺ overload. Furthermore, treatment with IH increased the expression of Cu/Zn SOD and Mn SOD, the total antioxidant capacity, and the activity of catalase. Blockade of the IH-increased ROS production abolished the protective effects of IH on the Ca²⁺ homeostasis and antioxidant defense capacity. Taken together, our findings suggest that IH protected the cardiomyocytes against H₂O₂- and I/R-induced oxidative stress and cell death through maintaining Ca²⁺ homeostasis as well as the mitochondrial membrane potential, and upregulation of antioxidant enzymes. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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16 pages, 1297 KiB

Open AccessArticle

Activation of Nrf2/HO-1 Pathway and Human Atherosclerotic Plaque Vulnerability: An In Vitro and In Vivo Study

by Susanna Fiorelli, Benedetta Porro, Nicola Cosentino, Alessandro Di Minno, Chiara Maria Manega, Franco Fabbiocchi, Giampaolo Niccoli, Francesco Fracassi, Simone Barbieri, Giancarlo Marenzi, Filippo Crea, Viviana Cavalca, Elena Tremoli and Sonia Eligini

Cells 2019, 8(4), 356; https://doi.org/10.3390/cells8040356 - 16 Apr 2019

Cited by 38 | Viewed by 5350

Abstract

Reactive oxygen species (ROS) induce nuclear factor erythroid 2–related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly [...] Read more.

Reactive oxygen species (ROS) induce nuclear factor erythroid 2–related factor 2 (Nrf2) activation as an adaptive defense mechanism, determining the synthesis of antioxidant molecules, including heme-oxygenase-1 (HO-1). HO-1 protects cells against oxidative injury, degrading free heme and inhibiting ROS production. HO-1 is highly expressed in macrophages during plaque growth. Macrophages are morpho-functionally heterogeneous, and the prevalence of a specific phenotype may influence the plaque fate. This heterogeneity has also been observed in monocyte-derived macrophages (MDMs), a model of macrophages infiltrating tissue. The study aims to assess oxidative stress status and Nrf2/HO-1 axis in MDM morphotypes obtained from healthy subjects and coronary artery disease (CAD) patients, in relation to coronary plaque features evaluated in vivo by optical coherence tomography (OCT). We found that MDMs of healthy subjects exhibited a lower oxidative stress status, lower Nrf2 and HO-1 levels as compared to CAD patients. High HO-1 levels in MDMs were associated with the presence of a higher macrophage content, a thinner fibrous cap, and a ruptured plaque with thrombus formation, detected by OCT analysis. These findings suggest the presence of a relationship between in vivo plaque characteristics and in vitro MDM profile, and may help to identify patients with rupture-prone coronary plaque. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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20 pages, 2340 KiB

Open AccessArticle

Beneficial Effects of Vitamins K and D3 on Redox Balance of Human Osteoblasts Cultured with Hydroxyapatite-Based Biomaterials

by Ewa Ambrożewicz, Marta Muszyńska, Grażyna Tokajuk, Grzegorz Grynkiewicz, Neven Žarković and Elżbieta Skrzydlewska

Cells 2019, 8(4), 325; https://doi.org/10.3390/cells8040325 - 8 Apr 2019

Cited by 23 | Viewed by 5148

Abstract

Hydroxyapatite-based biomaterials are commonly used in surgery to repair bone damage. However, the introduction of biomaterials into the body can cause metabolic alterations, including redox imbalance. Because vitamins D3 and K (K1, MK-4, MK-7) have pronounced osteoinductive, anti-inflammatory, and antioxidant properties, it is [...] Read more.

Hydroxyapatite-based biomaterials are commonly used in surgery to repair bone damage. However, the introduction of biomaterials into the body can cause metabolic alterations, including redox imbalance. Because vitamins D3 and K (K1, MK-4, MK-7) have pronounced osteoinductive, anti-inflammatory, and antioxidant properties, it is suggested that they may reduce the adverse effects of biomaterials. The aim of this study was to investigate the effects of vitamins D3 and K, used alone and in combination, on the redox metabolism of human osteoblasts (hFOB 1.19 cell line) cultured in the presence of hydroxyapatite-based biomaterials (Maxgraft, Cerabone, Apatos, and Gen-Os). Culturing of the osteoblasts in the presence of hydroxyapatite-based biomaterials resulted in oxidative stress manifested by increased production of reactive oxygen species and decrease of glutathione level and glutathione peroxidase activity. Such redox imbalance leads to lipid peroxidation manifested by an increase of 4-hydroxynonenal level, which is known to influence the growth of bone cells. Vitamins D3 and K were shown to help maintain redox balance and prevent lipid peroxidation in osteoblasts cultured with hydroxyapatite-based biomaterials. The strongest effect was observed for the combination of vitamin D3 and MK-7. Moreover, vitamins promoted growth of the osteoblasts, manifested by increased DNA biosynthesis. Therefore, it is suggested that the use of vitamins D3 and K may protect redox balance and support the growth of osteoblasts affected by hydroxyapatite-based biomaterials. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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10 pages, 526 KiB

Open AccessFeature PaperArticle

The Role of Acrolein and NADPH Oxidase in the Granulocyte-Mediated Growth-Inhibition of Tumor Cells

by Morana Jaganjac, Tanja Matijevic Glavan and Neven Zarkovic

Cells 2019, 8(4), 292; https://doi.org/10.3390/cells8040292 - 29 Mar 2019

Cited by 13 | Viewed by 3663

Abstract

Although granulocytes are the most abundant leukocytes in human blood, their involvement in the immune response against cancer is not well understood. While granulocytes are known for their “oxidative burst” when challenged with tumor cells, it is less known that oxygen-dependent killing of [...] Read more.

Although granulocytes are the most abundant leukocytes in human blood, their involvement in the immune response against cancer is not well understood. While granulocytes are known for their “oxidative burst” when challenged with tumor cells, it is less known that oxygen-dependent killing of tumor cells by granulocytes includes peroxidation of lipids in tumor cell membranes, yielding formation of reactive aldehydes like 4-hydroxynonenal (4-HNE) and acrolein. In the present work, we investigate the role of reactive aldehydes on cellular redox homeostasis and surface toll-like receptor 4 (TLR4) expression. We have further study the granulocyte-tumor cell intercellular redox signaling pathways. The data obtained show that granulocytes in the presence of 4-HNE and acrolein induce excessive ROS formation in tumor cells. Acrolein was also shown to induce granulocyte TLR4 expression. Furthermore, granulocyte-mediated antitumor effects were shown to be mediated via HOCl intracellular pathway by the action of NADPH oxidase. However, further studies are needed to understand interaction between TLR4 and granulocyte-tumor cell intercellular signaling pathways. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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12 pages, 1909 KiB

Open AccessCommunication

VAS2870 Inhibits Histamine-Induced Calcium Signaling and vWF Secretion in Human Umbilical Vein Endothelial Cells

by Pavel V. Avdonin, Elena Yu. Rybakova, Piotr P. Avdonin, Sergei K. Trufanov, Galina Yu. Mironova, Alexandra A. Tsitrina and Nikolay V. Goncharov

Cells 2019, 8(2), 196; https://doi.org/10.3390/cells8020196 - 23 Feb 2019

Cited by 12 | Viewed by 4749

Abstract

In this study, we investigated the effects of NAD(P)H oxidase (NOX) inhibitor VAS2870 (3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine) on the histamine-induced elevation of free cytoplasmic calcium concentration ([Ca²⁺]_i) and the secretion of von Willebrand factor (vWF) in human umbilical vein endothelial cells (HUVECs) [...] Read more.

In this study, we investigated the effects of NAD(P)H oxidase (NOX) inhibitor VAS2870 (3-benzyl-7-(2-benzoxazolyl)thio-1,2,3-triazolo[4,5-d]pyrimidine) on the histamine-induced elevation of free cytoplasmic calcium concentration ([Ca²⁺]_i) and the secretion of von Willebrand factor (vWF) in human umbilical vein endothelial cells (HUVECs) and on relaxation of rat aorta in response to histamine. At 10 μM concentration, VAS2870 suppressed the [Ca²⁺]_i rise induced by histamine. Inhibition was not competitive, with IC50 3.64 and 3.22 μM at 1 and 100 μM concentrations of histamine, respectively. There was no inhibition of [Ca²⁺]_i elevation by VAS2870 in HUVECs in response to the agonist of type 1 protease-activated receptor SFLLRN. VAS2870 attenuated histamine-induced secretion of vWF and did not inhibit basal secretion. VAS2870 did not change the degree of histamine-induced relaxation of rat aortic rings constricted by norepinephrine. We suggest that NOX inhibitors might be used as a tool for preventing thrombosis induced by histamine release from mast cells without affecting vasorelaxation. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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13 pages, 2157 KiB

Open AccessArticle

Increasing the TRPM2 Channel Expression in Human Neuroblastoma SH-SY5Y Cells Augments the Susceptibility to ROS-Induced Cell Death

by Xinfang An, Zixing Fu, Chendi Mai, Weiming Wang, Linyu Wei, Dongliang Li, Chaokun Li and Lin-Hua Jiang

Cells 2019, 8(1), 28; https://doi.org/10.3390/cells8010028 - 8 Jan 2019

Cited by 41 | Viewed by 6321

Abstract

Human neuroblastoma SH-SY5Y cells are a widely-used human neuronal cell model in the study of neurodegeneration. A recent study shows that, 1-methyl-4-phenylpyridine ion (MPP), which selectively causes dopaminergic neuronal death leading to Parkinson’s disease-like symptoms, can reduce SH-SY5Y cell viability by inducing H [...] Read more.

Human neuroblastoma SH-SY5Y cells are a widely-used human neuronal cell model in the study of neurodegeneration. A recent study shows that, 1-methyl-4-phenylpyridine ion (MPP), which selectively causes dopaminergic neuronal death leading to Parkinson’s disease-like symptoms, can reduce SH-SY5Y cell viability by inducing H₂O₂ generation and subsequent TRPM2 channel activation. MPP-induced cell death is enhanced by increasing the TRPM2 expression. By contrast, increasing the TRPM2 expression has also been reported to support SH-SY5Y cell survival after exposure to H₂O₂, leading to the suggestion of a protective role for the TRPM2 channel. To clarify the role of reactive oxygen species (ROS)-induced TRPM2 channel activation in SH-SY5Y cells, we generated a stable SH-SY5Y cell line overexpressing the human TRPM2 channel and examined cell death and cell viability after exposure to H₂O₂ in the wild-type and TRPM2-overexpressing SH-SY5Y cells. Exposure to H₂O₂ resulted in concentration-dependent cell death and reduction in cell viability in both cell types. TRPM2 overexpression remarkably augmented H₂O₂-induced cell death and reduction in cell viability. Furthermore, H₂O₂-induced cell death in both the wild-type and TRPM2-overexpressing cells was prevented by 2-APB, a TRPM2 inhibitor, and also by PJ34 and DPQ, poly(ADP-ribose) polymerase (PARP) inhibitors. Collectively, our results show that increasing the TRPM2 expression renders SH-SY5Y cells to be more susceptible to ROS-induced cell death and reinforce the notion that the TRPM2 channel plays a critical role in conferring ROS-induced cell death. It is anticipated that SH-SY5Y cells can be useful for better understanding the molecular and signaling mechanisms for ROS-induced TRPM2-mediated neurodegeneration in the pathogenesis of neurodegenerative diseases. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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Review

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16 pages, 22286 KiB

Open AccessReview

Roles of Toll-Like Receptors in Nitroxidative Stress in Mammals

by Yao Li, Shou-Long Deng, Zheng-Xing Lian and Kun Yu

Cells 2019, 8(6), 576; https://doi.org/10.3390/cells8060576 - 12 Jun 2019

Cited by 68 | Viewed by 8209

Abstract

Free radicals are important antimicrobial effectors that cause damage to DNA, membrane lipids, and proteins. Professional phagocytes produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute towards the destruction of pathogens. Toll-like receptors (TLRs) play a fundamental role in the [...] Read more.

Free radicals are important antimicrobial effectors that cause damage to DNA, membrane lipids, and proteins. Professional phagocytes produce reactive oxygen species (ROS) and reactive nitrogen species (RNS) that contribute towards the destruction of pathogens. Toll-like receptors (TLRs) play a fundamental role in the innate immune response and respond to conserved microbial products and endogenous molecules resulting from cellular damage to elicit an effective defense against invading pathogens, tissue injury, or cancer. In recent years, several studies have focused on how the TLR-mediated activation of innate immune cells leads to the production of pro-inflammatory factors upon pathogen invasion. Here, we review recent findings that indicate that TLRs trigger a signaling cascade that induces the production of reactive oxygen and nitrogen species. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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34 pages, 4385 KiB

Open AccessReview

5′,8-Cyclopurine Lesions in DNA Damage: Chemical, Analytical, Biological, and Diagnostic Significance

by Chryssostomos Chatgilialoglu, Carla Ferreri, Nicholas E. Geacintov, Marios G. Krokidis, Yuan Liu, Annalisa Masi, Vladimir Shafirovich, Michael A. Terzidis and Pawlos S. Tsegay

Cells 2019, 8(6), 513; https://doi.org/10.3390/cells8060513 - 28 May 2019

Cited by 47 | Viewed by 7012

Abstract

Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are tandem-type lesions observed among the DNA purine modifications and identified in mammalian cellular DNA in vivo. These lesions can be present in two diasteroisomeric forms, 5′R and 5′S, for each 2′-deoxyadenosine and 2′-deoxyguanosine moiety. They are [...] Read more.

Purine 5′,8-cyclo-2′-deoxynucleosides (cPu) are tandem-type lesions observed among the DNA purine modifications and identified in mammalian cellular DNA in vivo. These lesions can be present in two diasteroisomeric forms, 5′R and 5′S, for each 2′-deoxyadenosine and 2′-deoxyguanosine moiety. They are generated exclusively by hydroxyl radical attack to 2′-deoxyribose units generating C5′ radicals, followed by cyclization with the C8 position of the purine base. This review describes the main recent achievements in the preparation of the cPu molecular library for analytical and DNA synthesis applications for the studies of the enzymatic recognition and repair mechanisms, their impact on transcription and genetic instability, quantitative determination of the levels of lesions in various types of cells and animal model systems, and relationships between the levels of lesions and human health, disease, and aging, as well as the defining of the detection limits and quantification protocols. Full article

(This article belongs to the Special Issue Roles and Functions of ROS and RNS in Cellular Physiology and Pathology)

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