scholarly journals Reactive Oxygen Species: A Promising Therapeutic Target for SDHx-Mutated Pheochromocytoma and Paraganglioma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3769
Author(s):  
Katerina Hadrava Hadrava Vanova ◽  
Chunzhang Yang ◽  
Leah Meuter ◽  
Jiri Neuzil ◽  
Karel Pacak
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Cells ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Promising Therapeutic Target ◽  
Ros Accumulation ◽  
Intracellular Ros

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare neuroendocrine tumors derived from neural crest cells. Germline variants in approximately 20 PHEO/PGL susceptibility genes are found in about 40% of patients, half of which are found in the genes that encode succinate dehydrogenase (SDH). Patients with SDH subunit B (SDHB)-mutated PHEO/PGL exhibit a higher likelihood of developing metastatic disease, which can be partially explained by the metabolic cell reprogramming and redox imbalance caused by the mutation. Reactive oxygen species (ROS) are highly reactive molecules involved in a multitude of important signaling pathways. A moderate level of ROS production can help regulate cellular physiology; however, an excessive level of oxidative stress can lead to tumorigenic processes including stimulation of growth factor-dependent pathways and the induction of genetic instability. Tumor cells effectively exploit antioxidant enzymes in order to protect themselves against harmful intracellular ROS accumulation, which highlights the essential balance between ROS production and scavenging. Exploiting ROS accumulation can be used as a possible therapeutic strategy in ROS-scavenging tumor cells. Here, we focus on the role of ROS production in PHEO and PGL, predominantly in SDHB-mutated cases. We discuss potential strategies and approaches to anticancer therapies by enhancing ROS production in these difficult-to-treat tumors.

The Role of Reactive Oxygen Species in Tumor Treatment and its Impact on Bone Marrow Hematopoiesis

2020 ◽  
Vol 21 (5) ◽  
pp. 477-498
Author(s):  
Yongfeng Chen ◽  
Xingjing Luo ◽  
Zhenyou Zou ◽  
Yong Liang
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Oxidative Damage ◽  
Tumor Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Tumor Treatment ◽  
Normal Cells ◽  
Treatment And Prevention

Reactive oxygen species (ROS), an important molecule inducing oxidative stress in organisms, play a key role in tumorigenesis, tumor progression and recurrence. Recent findings on ROS have shown that ROS can be used to treat cancer as they accelerate the death of tumor cells. At present, pro-oxidant drugs that are intended to increase ROS levels of the tumor cells have been widely used in the clinic. However, ROS are a double-edged sword in the treatment of tumors. High levels of ROS induce not only the death of tumor cells but also oxidative damage to normal cells, especially bone marrow hemopoietic cells, which leads to bone marrow suppression and (or) other side effects, weak efficacy of tumor treatment and even threatening patients’ life. How to enhance the killing effect of ROS on tumor cells while avoiding oxidative damage to the normal cells has become an urgent issue. This study is a review of the latest progress in the role of ROS-mediated programmed death in tumor treatment and prevention and treatment of oxidative damage in bone marrow induced by ROS.

scholarly journals Production and scavenging of reactive oxygen species both affect reproductive success in male and female Drosophila melanogaster

2021 ◽  
Author(s):  
Biz R. Turnell ◽  
Luisa Kumpitsch ◽  
Klaus Reinhardt
Keyword(s):  
Reactive Oxygen Species ◽  
Drosophila Melanogaster ◽  
Reactive Oxygen ◽  
Cellular Aging ◽  
Ros Production ◽  
Oxygen Species ◽  
Wild Type ◽  
Ros Scavenging ◽  
Respiratory Pathway ◽  
Male And Female

AbstractSperm aging is accelerated by the buildup of reactive oxygen species (ROS), which cause oxidative damage to various cellular components. Aging can be slowed by limiting the production of mitochondrial ROS and by increasing the production of antioxidants, both of which can be generated in the sperm cell itself or in the surrounding somatic tissues of the male and female reproductive tracts. However, few studies have compared the separate contributions of ROS production and ROS scavenging to sperm aging, or to cellular aging in general. We measured reproductive fitness in two lines of Drosophila melanogaster genetically engineered to (1) produce fewer ROS via expression of alternative oxidase (AOX), an alternative respiratory pathway; or (2) scavenge fewer ROS due to a loss-of-function mutation in the antioxidant gene dj-1β. Wild-type females mated to AOX males had increased fecundity and longer fertility durations, consistent with slower aging in AOX sperm. Contrary to expectations, fitness was not reduced in wild-type females mated to dj-1β males. Fecundity and fertility duration were increased in AOX and decreased in dj-1β females, indicating that female ROS levels may affect aging rates in stored sperm and/or eggs. Finally, we found evidence that accelerated aging in dj-1β sperm may have selected for more frequent mating. Our results help to clarify the relative roles of ROS production and ROS scavenging in the male and female reproductive systems.

scholarly journals Somatic production of reactive oxygen species does not predict its production in sperm cells across Drosophila melanogaster lines

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Biz R. Turnell ◽  
Luisa Kumpitsch ◽  
Anne-Cécile Ribou ◽  
Klaus Reinhardt
Keyword(s):  
Reactive Oxygen Species ◽  
Drosophila Melanogaster ◽  
Reactive Oxygen ◽  
Future Research ◽  
Ros Production ◽  
Oxygen Species ◽  
Loss Of Function ◽  
Wild Type ◽  
Ros Scavenging ◽  
Transport Chain

Abstract Objective Sperm ageing has major evolutionary implications but has received comparatively little attention. Ageing in sperm and other cells is driven largely by oxidative damage from reactive oxygen species (ROS) generated by the mitochondria. Rates of organismal ageing differ across species and are theorized to be linked to somatic ROS levels. However, it is unknown whether sperm ageing rates are correlated with organismal ageing rates. Here, we investigate this question by comparing sperm ROS production in four lines of Drosophila melanogaster that have previously been shown to differ in somatic mitochondrial ROS production, including two commonly used wild-type lines and two lines with genetic modifications standardly used in ageing research. Results Somatic ROS production was previously shown to be lower in wild-type Oregon-R than in wild-type Dahomey flies; decreased by the expression of alternative oxidase (AOX), a protein that shortens the electron transport chain; and increased by a loss-of-function mutation in dj-1β, a gene involved in ROS scavenging. Contrary to predictions, we found no differences among these four lines in the rate of sperm ROS production. We discuss the implications of our results, the limitations of our study, and possible directions for future research.

scholarly journals FRI0370 DUAL OXIDASE MATURATION FACTOR 1 POSITIVELY REGULATES RANKL-INDUCED OSTEOCLASTOGENESIS VIA ACTIVATING REACTIVE OXYGEN SPECIES PRODUCTION AND TRAF6-MEDIATED SIGNALING

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 782.2-782
Author(s):  
C. H. Lee ◽  
C. H. Chung ◽  
Y. J. Choi ◽  
W. H. Yoo ◽  
J. Y. Kim ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Osteoclast Differentiation ◽  
Reactive Oxygen ◽  
Mouse Bone Marrow ◽  
Ros Production ◽  
Oxygen Species ◽  
Maturation Factor ◽  
Intracellular Ros ◽  
Dual Oxidase ◽  
Rankl Stimulation

Background:Reactive oxygen species (ROS) are one of the significant factors of chemical or physical cell signaling in a wide variety of cell types including skeletal cells. Receptor activator of NF-βB ligand (RANKL) induces generation of intracellular ROS, which act as second messengers in RANKL-mediated osteoclastogenesis. Dual oxidase maturation factor 1 (Duoxa1) was first identified as aDrosophilaNumb-interacting protein (NIP), and has been associated with the maturation of ROS generating enzymes including dual oxidases (Duox1 and Duox2). In the progression of osteoclast differentiation using mouse bone marrow-derived macrophages (BMMs), we identified that only Duoxa1 level showed an effective change upon RANKL stimulation, but not Duox1, Duox2, and Duoxa2.Objectives:we hypothesized that Duoxa1 could independently act as a second messenger for RANKL stimulation and regulate ROS production during osteoclast differentiation.Methods:Using siRNA or retrovirus transduction and knockdown of Duoxa1 via siRNAResults:Duoxa1 level gradually increased during RANKL-induced osteoclast differentiation. We found that Duoxa1 regulated RANKL-stimulated osteoclast formation and bone resorption positively. knockdown of Duoxa1 via siRNA decreased the RANKL-induced ROS production. During Duoxa1-related control of osteoclastogenesis, activation of tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-mediated early signaling molecules including MAPKs, Akt, IβB, Btk, and PLC 2 was affected, which sequentially modified the mRNA or protein expression levels of key transcription factors in osteoclastogenesis, such as c-Fos and NFATc1, as well as mRNA expression of osteoclast-specific markers including OSCAR, ATP6v0d2, and CtsK.Conclusion:Overall, our data indicate that Duoxa1 plays a crucial role in osteoclastogenesis via regulating RANKL-induced intracellular ROS production and activating TRAF6-mediated signaling.Disclosure of Interests:None declared

Reactive oxygen species modulate HIF-1 mediated PAI-1 expression: involvement of the GTPase Rac1

2003 ◽  
Vol 89 (05) ◽  
pp. 926-935 ◽  
Author(s):  
Utta Berchner-Pfannschmidt ◽  
Christoph Wotzlaw ◽  
Robbert Cool ◽  
Joachim Fandrey ◽  
Helmut Acker ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Plasminogen Activator Inhibitor ◽  
Dominant Negative ◽  
Mrna Levels ◽  
Ros Production ◽  
Oxygen Species ◽  
Plasminogen Activator Inhibitor 1 ◽  
Pai 1

SummaryThe hypoxia-inducible transcription factor HIF-1 mediates upregulation of plasminogen activator inhibitor-1 (PAI-1) expression under hypoxia. Reactive oxygen species (ROS) have also been implicated in PAI-1 gene expression. However, the role of ROS in HIF-1-mediated regulation of PAI-1 is not clear. We therefore investigated the role of the GTPase Rac1 which modulates ROS production in the pathway leading to HIF-1 and PAI-1 induction.Overexpression of constitutively activated (RacG12V) or dominant-negative (RacT17N) Rac1 increased or decreased, respectively, ROS production. In RacG12V-expressing cells, PAI-1 mRNA levels as well as HIF-1α nuclear presence were reduced under normoxia and hypoxia whereas expression of RacT17N resulted in opposite effects. Treatment with the antioxidant pyrrolidinedithiocarbamate or coexpression of the redox factor-1 restored HIF-1 and PAI-1 promoter activity in RacG12V-cells. In contrast, NFκB activation was enhanced in RacG12V-cells, but abolished by RacT17N. Thus, these findings suggest a mechanism explaining modified fibrinolysis and tissue remodeling in an oxidized environment.

scholarly journals The differential role of reactive oxygen species in early and late stages of cancer

2017 ◽  
Vol 313 (6) ◽  
pp. R646-R653 ◽  
Author(s):  
Mohamad Assi
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Reactive Oxygen ◽  
Pentose Phosphate ◽  
Oxygen Species ◽  
Redox Biology ◽  
Oxidative Damages ◽  
Late Stages

The large doses of vitamins C and E and β-carotene used to reduce reactive oxygen species (ROS) production and oxidative damages in cancerous tissue have produced disappointing and contradictory results. This therapeutic conundrum was attributed to the double-faced role of ROS, notably, their ability to induce either proliferation or apoptosis of cancer cells. However, for a ROS-inhibitory approach to be effective, it must target ROS when they induce proliferation rather than apoptosis. On the basis of recent advances in redox biology, this review underlined a differential regulation of prooxidant and antioxidant system, respective to the stage of cancer. At early precancerous and neoplastic stages, antioxidant activity decreases and ROS appear to promote cancer initiation via inducing oxidative damage and base pair substitution mutations in prooncogenes and tumor suppressor genes, such as RAS and TP53, respectively. Whereas in late stages of cancer progression, tumor cells escape apoptosis by producing high levels of intracellular antioxidants, like NADPH and GSH, via the pentose phosphate pathway to buffer the excessive production of ROS and related intratumor oxidative injuries. Therefore, antioxidants should be prohibited in patients with advanced stages of cancer and/or undergoing anticancer therapies. Interestingly, the biochemical and biophysical properties of some polyphenols allow them to selectively recognize tumor cells. This characteristic was exploited to design and deliver nanoparticles coated with low doses of polyphenols and containing chemotherapeutic drugs into tumor-bearing animals. First results are encouraging, which may revolutionize the conventional use of antioxidants in cancer.

scholarly journals Manganese-Oxidizing Antarctic Bacteria (Mn-Oxb) Release Reactive Oxygen Species (ROS) as Secondary Mn(II) Oxidation Mechanisms to Avoid Toxicity

Biology ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 1004
Author(s):  
Ignacio Jofré ◽  
Francisco Matus ◽  
Daniela Mendoza ◽  
Francisco Nájera ◽  
Carolina Merino
Keyword(s):  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Soil Formation ◽  
Ros Production ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Cell Protection ◽  
Temperature Dependent ◽  
Antarctic Soils ◽  
Dependent Mechanism

Manganese (Mn) oxidation is performed through oxidative Mn-oxidizing bacteria (MnOxb) as the main bio-weathering mechanism for Mn(III/IV) deposits during soil formation. However, with an increase in temperature, the respiration rate also increases, producing Reactive Oxygen Species (ROS) as by-products, which are harmful to microbial cells. We hypothesize that bacterial ROS oxidize Mn(II) to Mn(III/IV) as a secondary non-enzymatic temperature-dependent mechanism for cell protection. Fourteen MnOxb were isolated from Antarctic soils under the global warming effect, and peroxidase (PO) activity, ROS, and Mn(III/IV) production were evaluated for 120 h of incubation at 4 °C, 15 °C, and 30 °C. ROS contributions to Mn oxidation were evaluated in Arthrobacter oxydans under antioxidant (Trolox) and ROS-stimulated (menadione) conditions. The Mn(III/IV) concentration increased with temperature and positively correlated with ROS production. ROS scavenging with Trolox depleted the Mn oxidation, and ROS-stimulant increased the Mn precipitation in A. oxydans. Increasing the Mn(II) concentration caused a reduction in the membrane potential and bacterial viability, which resulted in Mn precipitation on the bacteria surface. In conclusion, bacterial ROS production serves as a complementary non-enzymatic temperature-dependent mechanism for Mn(II) oxidation as a response in warming environments.

scholarly journals Graphene and graphene oxide induce ROS production in human HaCaT skin keratinocytes: the role of xanthine oxidase and NADH dehydrogenase

Nanoscale ◽  
2018 ◽  
Vol 10 (25) ◽  
pp. 11820-11830 ◽  
Author(s):  
Marco Pelin ◽  
Laura Fusco ◽  
Cristina Martín ◽  
Silvio Sosa ◽  
Javier Frontiñán-Rubio ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Graphene Oxide ◽  
Xanthine Oxidase ◽  
Nadh Dehydrogenase ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Depolarization ◽  
Skin Keratinocytes

Graphene based nanomaterials induce a reactive oxygen species-mediated mitochondrial depolarization, caused by the activation of NADH dehydrogenase and xanthine oxidase.

scholarly journals Targeting Reactive Oxygen Species in Atherosclerosis via Chinese Herbal Medicines

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Leyi Zhang ◽  
Jiaqin Huang ◽  
Danli Zhang ◽  
Xiaojing Lei ◽  
Yan Ma ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Population Aging ◽  
Herbal Medicines ◽  
Reactive Oxygen ◽  
Major Type ◽  
Oxygen Species ◽  
Chinese Herbal ◽  
Natural Medicine ◽  
Intracellular Ros

Cardio-cerebrovascular disease (CCVD) has become the leading cause of human mortality with the coming acceleration of global population aging. Atherosclerosis is among the most common pathological changes in CCVDs. It is also a multifactorial disorder; oxidative stress caused by excessive production of reactive oxygen species (ROS) has become an important mechanism of atherosclerosis. Chinese herbal medicine (CHM) is a major type of natural medicine that has made great contributions to human health. CHMs are increasingly used in the auxiliary clinical treatment of atherosclerosis. Although their mechanism of action is unclear, CHMs can exert a variety of antiatherosclerosis effects by regulating intracellular ROS. In this review, we discussed the mechanism of ROS regulation in atherosclerosis and analyzed the role of CHMs in the treatment of atherosclerosis via ROS.

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