scholarly journals Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5252
Author(s):  
Yasuyoshi Miyata ◽  
Yuta Mukae ◽  
Junki Harada ◽  
Tsuyoshi Matsuda ◽  
Kensuke Mitsunari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Reactive Oxygen ◽  
Chemotherapeutic Agents ◽  
Malignant Neoplasms ◽  
Oxygen Species ◽  
Efficient Treatment ◽  
Intracellular Ros

Oxidative stress plays an important role in cellular processes. Consequently, oxidative stress also affects etiology, progression, and response to therapeutics in various pathological conditions including malignant tumors. Oxidative stress and associated outcomes are often brought about by excessive generation of reactive oxygen species (ROS). Accumulation of ROS occurs due to dysregulation of homeostasis in an otherwise strictly controlled physiological condition. In fact, intracellular ROS levels are closely associated with the pathological status and outcome of numerous diseases. Notably, mitochondria are recognized as the critical regulator and primary source of ROS. Damage to mitochondria increases mitochondrial ROS (mROS) production, which leads to an increased level of total intracellular ROS. However, intracellular ROS level may not always reflect mROS levels, as ROS is not only produced by mitochondria but also by other organelles such as endoplasmic reticulum and peroxisomes. Thus, an evaluation of mROS would help us to recognize the biological and pathological characteristics and predictive markers of malignant tumors and develop efficient treatment strategies. In this review, we describe the pathological significance of mROS in malignant neoplasms. In particular, we show the association of mROS-related signaling in the molecular mechanisms of chemically synthesized and natural chemotherapeutic agents and photodynamic therapy.

scholarly journals The Helicobacter pylori CZB Cytoplasmic Chemoreceptor TlpD Forms an Autonomous Polar Chemotaxis Signaling Complex That Mediates a Tactic Response to Oxidative Stress

2016 ◽  
Vol 198 (11) ◽  
pp. 1563-1575 ◽  
Author(s):  
Kieran D. Collins ◽  
Tessa M. Andermann ◽  
Jenny Draper ◽  
Lisa Sanders ◽  
Susan M. Williams ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Helicobacter Pylori ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Host Cells ◽  
Oxygen Species ◽  
Content Type ◽  
Signaling Complex ◽  
H Pylori

ABSTRACTCytoplasmic chemoreceptors are widespread among prokaryotes but are far less understood than transmembrane chemoreceptors, despite being implicated in many processes. One such cytoplasmic chemoreceptor isHelicobacter pyloriTlpD, which is required for stomach colonization and drives a chemotaxis response to cellular energy levels. Neither the signals sensed by TlpD nor its molecular mechanisms of action are known. We report here that TlpD functions independently of the other chemoreceptors. When TlpD is the sole chemoreceptor, it is able to localize to the pole and recruits CheW, CheA, and at least two CheV proteins to this location. It loses the normal membrane association that appears to be driven by interactions with other chemoreceptors and with CheW, CheV1, and CheA. These results suggest that TlpD can form an autonomous signaling unit. We further determined that TlpD mediates a repellent chemotaxis response to conditions that promote oxidative stress, including being in the presence of iron, hydrogen peroxide, paraquat, and metronidazole. Last, we found that all testedH. pyloristrains express TlpD, whereas other chemoreceptors were present to various degrees. Our data suggest a model in which TlpD coordinates a signaling complex that responds to oxidative stress and may allowH. pylorito avoid areas of the stomach with high concentrations of reactive oxygen species.IMPORTANCEHelicobacter pylorisenses its environment with proteins called chemoreceptors. Chemoreceptors integrate this sensory information to affect flagellum-based motility in a process called chemotaxis. Chemotaxis is employed during infection and presumably aidsH. pyloriin encountering and colonizing preferred niches. A cytoplasmic chemoreceptor named TlpD is particularly important in this process, and we report here that this chemoreceptor is able to operate independently of other chemoreceptors to organize a chemotaxis signaling complex and mediate a repellent response to oxidative stress conditions.H. pyloriencounters and must cope with oxidative stress during infection due to oxygen and reactive oxygen species produced by host cells. TlpD's repellent response may allow the bacteria to escape niches experiencing inflammation and elevated reactive oxygen species (ROS) production.

scholarly journals Sperm oxidative stress: clinical significance and management

2021 ◽  
pp. 19-27
Author(s):  
S. I. Gamidov ◽  
T. V. Shatylko ◽  
A. Yu. Popova ◽  
N. G. Gasanov ◽  
R. S. Gamidov
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reproductive System ◽  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Reactive Oxygen ◽  
Reproductive Technologies ◽  
Male Reproductive System ◽  
Antioxidant Systems ◽  
Oxygen Species

Oxidative stress is one of the leading causes of sperm dysfunction. Excessive amounts of reactive oxygen species can damage sperm membranes and disrupt their DNA integrity, which affects not only the likelihood of getting pregnant naturally, but also the clinical outcomes of assisted reproductive technologies and the risk of miscarriage. Sperm cells are extremely vulnerable to oxidative stress, given the limited functional reserve of their antioxidant systems and the DNA repair apparatus. Lifestyle factors, most of which are modifiable, often trigger generation of reactive oxygen species.  Both the lifestyle modification and use of antioxidant dietary supplements are adequate and compatible ways to combat male oxidative stress-associated infertility. The search for other internal and external sources of reactive oxygen species, the identification of the etiology of oxidative stress and treatment of respective diseases are necessary for the successful regulation of redox processes in the male reproductive system in clinical practice, which is required not only to overcome infertility, but also to prevent induced epigenetic disorders in subsequent generations. The article presents the analysis of the molecular mechanisms of male idiopathic infertility. The authors provide an overview of how to prevent oxidative stress as one of the causes of subfebrile fever. The article provides an overview of modern therapeutics, as well as the options for eliminating the consequences of the effect of reactive oxygen species on spermatogenesis and male reproductive system in general.

scholarly journals Elesclomol-induced increase of mitochondrial reactive oxygen species impairs glioblastoma stem-like cell survival and tumor growth

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Mariachiara Buccarelli ◽  
Quintino Giorgio D’Alessandris ◽  
Paola Matarrese ◽  
Cristiana Mollinari ◽  
Michele Signore ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Strong Increase ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, characterized by a poor prognosis mainly due to recurrence and therapeutic resistance. It has been widely demonstrated that glioblastoma stem-like cells (GSCs), a subpopulation of tumor cells endowed with stem-like properties is responsible for tumor maintenance and progression. Moreover, it has been demonstrated that GSCs contribute to GBM-associated neovascularization processes, through different mechanisms including the transdifferentiation into GSC-derived endothelial cells (GdECs). Methods In order to identify druggable cancer-related pathways in GBM, we assessed the effect of a selection of 349 compounds on both GSCs and GdECs and we selected elesclomol (STA-4783) as the most effective agent in inducing cell death on both GSC and GdEC lines tested. Results Elesclomol has been already described to be a potent oxidative stress inducer. In depth investigation of the molecular mechanisms underlying GSC and GdEC response to elesclomol, confirmed that this compound induces a strong increase in mitochondrial reactive oxygen species (ROS) in both GSCs and GdECs ultimately leading to a non-apoptotic copper-dependent cell death. Moreover, combined in vitro treatment with elesclomol and the alkylating agent temozolomide (TMZ) enhanced the cytotoxicity compared to TMZ alone. Finally, we used our experimental model of mouse brain xenografts to test the combination of elesclomol and TMZ and confirmed their efficacy in vivo. Conclusions Our results support further evaluation of therapeutics targeting oxidative stress such as elesclomol with the aim of satisfying the high unmet medical need in the management of GBM.

scholarly journals Molecular Interactions Between Reactive Oxygen Species and Autophagy in Kidney Disease

2019 ◽  
Vol 20 (15) ◽  
pp. 3791 ◽  
Author(s):  
Gur P. Kaushal ◽  
Kiran Chandrashekar ◽  
Luis A. Juncos
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Kidney Disease ◽  
Oxidative Damage ◽  
Molecular Interactions ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Reactive Oxygen ◽  
Renal Diseases ◽  
Oxygen Species

Reactive oxygen species (ROS) are highly reactive signaling molecules that maintain redox homeostasis in mammalian cells. Dysregulation of redox homeostasis under pathological conditions results in excessive generation of ROS, culminating in oxidative stress and the associated oxidative damage of cellular components. ROS and oxidative stress play a vital role in the pathogenesis of acute kidney injury and chronic kidney disease, and it is well documented that increased oxidative stress in patients enhances the progression of renal diseases. Oxidative stress activates autophagy, which facilitates cellular adaptation and diminishes oxidative damage by degrading and recycling intracellular oxidized and damaged macromolecules and dysfunctional organelles. In this review, we report the current understanding of the molecular regulation of autophagy in response to oxidative stress in general and in the pathogenesis of kidney diseases. We summarize how the molecular interactions between ROS and autophagy involve ROS-mediated activation of autophagy and autophagy-mediated reduction of oxidative stress. In particular, we describe how ROS impact various signaling pathways of autophagy, including mTORC1-ULK1, AMPK-mTORC1-ULK1, and Keap1-Nrf2-p62, as well as selective autophagy including mitophagy and pexophagy. Precise elucidation of the molecular mechanisms of interactions between ROS and autophagy in the pathogenesis of renal diseases may identify novel targets for development of drugs for preventing renal injury.

scholarly journals Dual and Opposite Roles of Reactive Oxygen Species (ROS) in Chagas Disease: Beneficial on the Pathogen and Harmful on the Host

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Edio Maldonado ◽  
Diego A. Rojas ◽  
Sebastian Morales ◽  
Vicente Miralles ◽  
Aldo Solari
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Oxidative Damage ◽  
Chagas Disease ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Parasite Growth ◽  
Oxygen Species ◽  
Chronic Stage ◽  
Mitochondrial Ros

Chagas disease is a neglected tropical disease, which affects an estimate of 6-7 million people worldwide. Chagas disease is caused by Trypanosoma cruzi, which is a eukaryotic flagellate unicellular organism. At the primary infection sites, these parasites are phagocytized by macrophages, which produce reactive oxygen species (ROS) in response to the infection with T. cruzi. The ROS produce damage to the host tissues; however, macrophage-produced ROS is also used as a signal for T. cruzi proliferation. At the later stages of infection, mitochondrial ROS is produced by the infected cardiomyocytes that contribute to the oxidative damage, which persists at the chronic stage of the disease. The oxidative damage leads to a functional impairment of the heart. In this review article, we will discuss the mechanisms by which T. cruzi is able to deal with the oxidative stress and how this helps the parasite growth at the acute phase of infection and how the oxidative stress affects the cardiomyopathy at the chronic stage of the Chagas disease. We will describe the mechanisms used by the parasite to deal with ROS and reactive nitrogen species (RNS) through the trypanothione and the mechanisms used to repair the damaged DNA. Also, a description of the events produced by ROS at the acute and chronic stages of the disease is presented. Lastly, we discuss the benefits of ROS for T. cruzi growth and proliferation and the possible mechanisms involved in this phenomenon. Hypothesis is put forward to explain the molecular mechanisms by which ROS triggers parasite growth and proliferation and how ROS is able to produce a long persisting damage on cardiomyocytes even in the absence of the parasite.

scholarly journals Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Noah C. Jenkins ◽  
Douglas Grossman
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Cell Types ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Potential Alternative ◽  
Oxidative Insult ◽  
Increased Susceptibility

We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS) than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS) may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

scholarly journals Molecular Mechanisms Involved in Oxidative Stress-Associated Liver Injury Induced by Chinese Herbal Medicine: An Experimental Evidence-Based Literature Review and Network Pharmacology Study

2018 ◽  
Vol 19 (9) ◽  
pp. 2745 ◽  
Author(s):  
Cheng Zhang ◽  
Ning Wang ◽  
Yu Xu ◽  
Hor-Yue Tan ◽  
Sha Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Oxygen Species ◽  
Hepatic Disorder ◽  
Redox Biology ◽  
Pathological Mechanism

Oxidative stress, defined as a disequilibrium between pro-oxidants and antioxidants, can result in histopathological lesions with a broad spectrum, ranging from asymptomatic hepatitis to hepatocellular carcinoma in an orchestrated manner. Although cells are equipped with sophisticated strategies to maintain the redox biology under normal conditions, the abundance of redox-sensitive xenobiotics, such as medicinal ingredients originated from herbs or animals, can dramatically invoke oxidative stress. Growing evidence has documented that the hepatotoxicity can be triggered by traditional Chinese medicine (TCM) during treating various diseases. Meanwhile, TCM-dependent hepatic disorder represents a strong correlation with oxidative stress, especially the persistent accumulation of intracellular reactive oxygen species. Of note, since TCM-derived compounds with their modulated targets are greatly diversified among themselves, it is complicated to elaborate the potential pathological mechanism. In this regard, data mining approaches, including network pharmacology and bioinformatics enrichment analysis have been utilized to scientifically disclose the underlying pathogenesis. Herein, top 10 principal TCM-modulated targets for oxidative hepatotoxicity including superoxide dismutases (SOD), malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), glutathione peroxidase (GPx), Bax, caspase-3, Bcl-2, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nitric oxide (NO) have been identified. Furthermore, hepatic metabolic dysregulation may be the predominant pathological mechanism involved in TCM-induced hepatotoxic impairment.

90 INTRACELLULAR REACTIVE OXYGEN SPECIES IN BOVINE EMBRYOS CULTURED IN VITRO WITH CATALASE UNDER VARIOUS OXYGEN TENSIONS

2012 ◽  
Vol 24 (1) ◽  
pp. 157 ◽  
Author(s):  
N. A. S. Rocha ◽  
B. C. S. Leão ◽  
M. F. Accorsi ◽  
G. Z. Mingoti
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Embryonic Development ◽  
Embryo Development ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Bovine Embryos ◽  
Intracellular Ros ◽  
Oxygen Tensions

The production of reactive oxygen species (ROS), such as superoxide anion (O2–), hydroxyl radical (OH–) hydrogen peroxide (H2O2) and organic peroxides, is a normal process that occurs in the cellular mitochondrial respiratory chain. The high oxygen tension in in vitro culture (IVC) conditions is believed to induce oxidative stress, as a result of increase in ROS intracellular production, that can be correlated with embryonic developmental failure. Supplementation with antioxidants during IVC appears to increase the resistance of bovine embryos to the oxidative stress and consequently improve embryo development. The aim of this study was to evaluate the effects of antioxidant (catalase) and oxygen tensions during IVC on the embryonic development and quantification of intracellular ROS. Cumulus–oocyte complexes (COC; n = 337) were in vitro matured (IVM) in TCM-199 supplemented with 0.2 mM pyruvate, 25 mM sodium bicarbonate, 75 μg mL–1 gentamicin, 10% FCS and hormones for 24 h at 38.5°C and 5% CO2 in air. Then they were fertilized and the presumptive zygotes were cultured in SOFaa medium without (control) or with 100 UI catalase (CAT) for 7 days at 38.5°C in one of 2 types of humified atmosphere: 5% CO2 in air (≈20% O2) or in gaseous mixture (7% O2, 5% CO2 and 88% N2). The cleavage rate was evaluated at 72 hours post-insemination (hpi) and the embryonic development at 168 hpi. At this time, the level of intracellular ROS was measured using the fluorescent probe 6-carboxy-2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA; Molecular Probes, Invitrogen, Oakville, Canada), at 5 μM (Bain et al. 2011 Reprod. Fertil. Dev. 23, 561–575). Stained embryos were imaged immediately using an inverted microscope and analysed by Q-Capture Pro image software (QImaging, Surrey, BC, Canada). The signal intensity values of embryos were subtracted by the average of backgrounds in the images. Embryo development was analysed by chi-squared test and means of the intensity of fluorescence were compared by ANOVA followed by Tukey's test (P < 0.05). The cleavage rates were 84.04%a (control 20% O2), 77.55%a (CAT 20% O2), 77.03%a (control 7% O2) and 71.83%a (CAT 7% O2). The embryonic development rates were 40.43%a (control 20% O2), 33.67%a (CAT 20% O2), 20.27%b (control 7% O2) and 16.90%b (CAT 7% O2). The fluorescent intensity were 3.9 ± 0.4a (control 20% O2), 1.8 ± 0.2b (CAT 20% O2), 2.7 ± 0.2ab (control 7% O2) and 2.8 ± 0.2ab (CAT 7% O2). Although catalase did not significantly affect blastocyst frequencies (P > 0.05), embryo development was adversely affected by reduced O2 tension (P < 0.05). H2DCFDA staining indicated a significant (P < 0.05) reduction in the levels of intracellular ROS within embryos cultured with catalase under 20% O2 compared with the control group in the same O2 tension. Additionally, a consistent but insignificant reduction in intracellular ROS within embryos cultured under 7% O2 was found. We can conclude that supplementation with catalase to IVC medium at 20% O2 is suitable for lowering intracellular ROS levels in IVP bovine embryos, without lowering the rates of blastocysts production. This finding corroborates with theory that antioxidants are beneficial to embryo quality. Alta Genetics Brazil, Deoxi Biotecnologia.

Mechanisms and Treatments of Oxidative Stress in Atrial Fibrillation

2018 ◽  
Vol 24 (26) ◽  
pp. 3062-3071 ◽  
Author(s):  
Xiaomeng Ren ◽  
Xiaofeng Wang ◽  
Mengchen Yuan ◽  
Chao Tian ◽  
Huilong Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Atrial Fibrillation ◽  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Stress Markers ◽  
Related Substances ◽  
Health Care Burden ◽  
Oxide Synthase

Atrial fibrillation (AF) is a frequent cardiac arrhythmia. It is a common major cause of serious diseases and is an increasing health-care burden. AF is associated with an excess amount of reactive oxygen species. In this review, we summarize several possible reactive oxygen species pathways that induce AF based on atrial electrical and structural remodeling data. The sources and factors implicated in AF-related oxidative stress include NADPH oxidase activation, calcium overloading and mitochondrial damage, angiotensin system activation, nitric oxide synthase uncoupling, and xanthine oxidase activation-associated cardiovascular conditions. Scavenging oxidative stress markers and related substances are essential aspects of these molecular mechanisms, and may be a therapeutic target in AF.

scholarly journals Adrenomedullin Regulates Cellular Glutathione Content via Modulation of γ-Glutamate-Cysteine Ligase Catalytic Subunit Expression

Endocrinology ◽  
2006 ◽  
Vol 147 (3) ◽  
pp. 1357-1364 ◽  
Author(s):  
Jee-Youn Kim ◽  
Ji-Hye Yim ◽  
Jin-Ho Cho ◽  
Jin-Hwan Kim ◽  
Jeong-Hun Ko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Reactive Oxygen ◽  
Catalytic Subunit ◽  
Oxygen Species ◽  
Glutamate Cysteine Ligase ◽  
Hypoxic Injury ◽  
Wide Range

Adrenomedullin (AM) participates in a wide range of physiological and pathological processes including vasorelaxation, angiogenesis, cancer promotion, and apoptosis. Recently, it has been reported that AM protects a variety of cells against oxidative stress induced by stressors such as hypoxia, ischemia/reperfusion, and hydrogen peroxide through the phosphatidylinositol 3-kinase (PI3K)-dependent pathway. However, the molecular mechanisms underlying the pathway of cell survival against hypoxic injury are largely unknown. In an effort to investigate the survival mechanism against hypoxic injury, we studied the effects of AM on cellular levels of reactive oxygen species, well-known mediators of cell death after oxidative stress, and the mechanism involved in the regulation of reactive oxygen species levels. Here, we show that AM increases γ-glutamate-cysteine ligase (γ-GCL) activity under both hypoxic and normoxic conditions, resulting in an up-regulation of cellular glutathione levels to more than 2-fold higher than basal expression. In addition, we demonstrate that AM induces concentration-dependent expression of the catalytic subunit of γ-GCL (γ-GCLC) at the mRNA and protein levels through the activation of the γ-GCLC promoter fragment sequence from −597 to −320. However, when treated with the PI3K inhibitors, the effects of AM on γ-GCLC expression were completely abrogated, suggesting that a PI3K pathway linked AM with the transcriptional activation of the γ-GCLC promoter. Taken together, our data suggests that AM participates in the regulation of cellular redox status via glutathione synthesis. These results may explain, in part, the mechanism by which AM protects cells against oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document