scholarly journals Roles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Chenglin Han ◽  
Zilong Wang ◽  
Yingkun Xu ◽  
Shuxiao Chen ◽  
Yuqing Han ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Antioxidant Genes ◽  
Beneficial Effects ◽  
Cell Functions ◽  
Incidence And Mortality ◽  
Intracellular Ros ◽  
High Incidence

Prostate cancer (PCa), known as a heterogenous disease, has a high incidence and mortality rate around the world and seriously threatens public health. As an inevitable by-product of cellular metabolism, reactive oxygen species (ROS) exhibit beneficial effects by regulating signaling cascades and homeostasis. More and more evidence highlights that PCa is closely associated with age, and high levels of ROS are driven through activation of several signaling pathways with age, which facilitate the initiation, development, and progression of PCa. Nevertheless, excessive amounts of ROS result in harmful effects, such as genotoxicity and cell death. On the other hand, PCa cells adaptively upregulate antioxidant genes to detoxify from ROS, suggesting that a subtle balance of intracellular ROS levels is required for cancer cell functions. The current review discusses the generation and biological roles of ROS in PCa and provides new strategies based on the regulation of ROS for the treatment of PCa.

scholarly journals Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 320 ◽  
Author(s):  
Shuya Kasai ◽  
Sunao Shimizu ◽  
Yota Tatara ◽  
Junsei Mimura ◽  
Ken Itoh
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Physiological Stress ◽  
Reactive Oxygen ◽  
Negative Regulator ◽  
Endurance Capacity ◽  
Oxygen Species ◽  
Antioxidant Genes ◽  
Beneficial Effects ◽  
Quantity Control

Reactive oxygen species (ROS) are byproducts of aerobic respiration and signaling molecules that control various cellular functions. Nrf2 governs the gene expression of endogenous antioxidant synthesis and ROS-eliminating enzymes in response to various electrophilic compounds that inactivate the negative regulator Keap1. Accumulating evidence has shown that mitochondrial ROS (mtROS) activate Nrf2, often mediated by certain protein kinases, and induce the expression of antioxidant genes and genes involved in mitochondrial quality/quantity control. Mild physiological stress, such as caloric restriction and exercise, elicits beneficial effects through a process known as “mitohormesis”. Exercise induces NOX4 expression in the heart, which activates Nrf2 and increases endurance capacity. Mice transiently depleted of SOD2 or overexpressing skeletal muscle-specific UCP1 exhibit Nrf2-mediated antioxidant gene expression and PGC1α-mediated mitochondrial biogenesis. ATF4 activation may induce a transcriptional program that enhances NADPH synthesis in the mitochondria and might cooperate with the Nrf2 antioxidant system. In response to severe oxidative stress, Nrf2 induces Klf9 expression, which represses mtROS-eliminating enzymes to enhance cell death. Nrf2 is inactivated in certain pathological conditions, such as diabetes, but Keap1 down-regulation or mtROS elimination rescues Nrf2 expression and improves the pathology. These reports aid us in understanding the roles of Nrf2 in pathophysiological alterations involving mtROS.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure

2019 ◽  
Vol 18 (9) ◽  
pp. 1313-1322 ◽  
Author(s):  
Manjula Devi Ramamoorthy ◽  
Ashok Kumar ◽  
Mahesh Ayyavu ◽  
Kannan Narayanan Dhiraviam
Keyword(s):  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Membrane Potential ◽  
Cancer Cells ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells

Background: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. Methods: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. Results: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. Conclusion: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

scholarly journals PRDX1 is essential for the viability and maintenance of reactive oxygen species in chicken DT40

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Takahito Moriwaki ◽  
Akari Yoshimura ◽  
Yuki Tamari ◽  
Hiroyuki Sasanuma ◽  
Shunichi Takeda ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Death ◽  
Intracellular Signaling ◽  
Reactive Oxygen ◽  
Fine Tuning ◽  
Oxygen Species ◽  
Ros Homeostasis ◽  
Intracellular Ros ◽  
Chromosomal Breaks ◽  
Dt40 Cells

Abstract Background Peroxiredoxin 1 (PRDX1) is a member of a ubiquitous family of thiol peroxidases that catalyze the reduction of peroxides, including hydrogen peroxide. It functions as an antioxidant enzyme, similar to catalase and glutathione peroxidase. PRDX1 was recently shown act as a sensor of reactive oxygen species (ROS) and play a role in ROS-dependent intracellular signaling pathways. To investigate its physiological functions, PRDX1 was conditionally disrupted in chicken DT40 cells in the present study. Results The depletion of PRDX1 resulted in cell death with increased levels of intracellular ROS. PRDX1-depleted cells did not show the accumulation of chromosomal breaks or sister chromatid exchange (SCE). These results suggest that cell death in PRDX1-depleted cells was not due to DNA damage. 2-Mercaptoethanol protected against cell death in PRDX1-depleted cells and also suppressed elevations in ROS. Conclusions PRDX1 is essential in chicken DT40 cells and plays an important role in maintaining intracellular ROS homeostasis (or in the fine-tuning of cellular ROS levels). Cells deficient in PRDX1 may be used as an endogenously deregulated ROS model to elucidate the physiological roles of ROS in maintaining proper cell growth.

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

A 60-Hz sinusoidal magnetic field induces apoptosis of prostate cancer cells through reactive oxygen species

2008 ◽  
Vol 84 (11) ◽  
pp. 945-955 ◽  
Author(s):  
Eui Kwan Koh ◽  
Byung-Kyu Ryu ◽  
Dong-Young Jeong ◽  
Iel-Soo Bang ◽  
Myung Hee Nam ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Prostate Cancer ◽  
Reactive Oxygen Species ◽  
Cancer Cells ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Prostate Cancer Cells ◽  
Sinusoidal Magnetic Field

Reactive oxygen species formation in the transition to hypoxia in skeletal muscle

2005 ◽  
Vol 289 (1) ◽  
pp. C207-C216 ◽  
Author(s):  
Li Zuo ◽  
Thomas L. Clanton
Keyword(s):  
Reactive Oxygen Species ◽  
Skeletal Muscle ◽  
Acute Hypoxia ◽  
Low Frequency ◽  
Metabolic Stress ◽  
Reactive Oxygen ◽  
Fluorescence Signal ◽  
Oxygen Species ◽  
Peroxidase Mimic ◽  
Intracellular Ros

Many tissues produce reactive oxygen species (ROS) during reoxygenation after hypoxia or ischemia; however, whether ROS are formed during hypoxia is controversial. We tested the hypothesis that ROS are generated in skeletal muscle during exposure to acute hypoxia before reoxygenation. Isolated rat diaphragm strips were loaded with dihydrofluorescein-DA (Hfluor-DA), a probe that is oxidized to fluorescein (Fluor) by intracellular ROS. Changes in fluorescence due to Fluor, NADH, and FAD were measured using a tissue fluorometer. The system had a detection limit of 1 μM H2O2 applied to the muscle superfusate. When the superfusion buffer was changed rapidly from 95% O2 to 0%, 5%, 21%, or 40% O2, transient elevations in Fluor were observed that were proportional to the rise in NADH fluorescence and inversely proportional to the level of O2 exposure. This signal could be inhibited completely with 40 μM ebselen, a glutathione peroxidase mimic. After brief hypoxia exposure (10 min) or exposure to brief periods of H2O2, the fluorescence signal returned to baseline. Furthermore, tissues loaded with the oxidized form of the probe (Fluor-DA) showed a similar pattern of response that could be inhibited with ebselen. These results suggest that Fluor exists in a partially reversible redox state within the tissue. When Hfluor-loaded tissues were contracted with low-frequency twitches, Fluor emission and NADH emission were significantly elevated in a way that resembled the hypoxia-induced signal. We conclude that in the transition to low intracellular Po2, a burst of intracellular ROS is formed that may have functional implications regarding skeletal muscle O2-sensing systems and responses to acute metabolic stress.

Activation of the JAK-STAT pathway by reactive oxygen species

1998 ◽  
Vol 275 (6) ◽  
pp. C1640-C1652 ◽  
Author(s):  
Amy R. Simon ◽  
Usha Rai ◽  
Barry L. Fanburg ◽  
Brent H. Cochran
Keyword(s):  
Reactive Oxygen Species ◽  
Mammalian Cells ◽  
Reactive Oxygen ◽  
Buthionine Sulfoximine ◽  
Early Response ◽  
Carcinoma Cells ◽  
Oxygen Species ◽  
Intracellular Ros ◽  
Diphenylene Iodonium ◽  
Stat Pathway

Reactive oxygen species (ROS) play an important role in the pathogenesis of many human diseases, including the acute respiratory distress syndrome, Parkinson’s disease, pulmonary fibrosis, and Alzheimer’s disease. In mammalian cells, several genes known to be induced during the immediate early response to growth factors, including the protooncogenes c- fos and c- myc, have also been shown to be induced by ROS. We show that members of the STAT family of transcription factors, including STAT1 and STAT3, are activated in fibroblasts and A-431 carcinoma cells in response to H2O2. This activation occurs within 5 min, can be inhibited by antioxidants, and does not require protein synthesis. STAT activation in these cell lines is oxidant specific and does not occur in response to superoxide- or nitric oxide-generating stimuli. Buthionine sulfoximine, which depletes intracellular glutathione, also activates the STAT pathway. Moreover, H2O2stimulates the activity of the known STAT kinases JAK2 and TYK2. Activation of STATs by platelet-derived growth factor (PDGF) is significantly inhibited by N-acetyl-l-cysteine and diphenylene iodonium, indicating that ROS production contributes to STAT activation in response to PDGF. These findings indicate that the JAK-STAT pathway responds to intracellular ROS and that PDGF uses ROS as a second messenger to regulate STAT activation.

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