Involvement of reactive oxygen species in ionizing radiation–induced upregulation of cell surface Toll-like receptor 2 and 4 expression in human monocytic cells

Abstract Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns and are indispensable for antibacterial and antiviral immunity. Our previous report showed that ionizing radiation increases the cell surface expressions of TLR2 and TLR4 and enhances their responses to agonists in human monocytic THP1 cells. The present study investigated how ionizing radiation increases the cell surface expressions of TLR2 and TLR4 in THP1 cells. The THP1 cells treated or not treated with pharmaceutical agents such as cycloheximide and N-acetyl-L-cysteine (NAC) were exposed to X-ray irradiation, following which the expressions of TLRs and mitogen-activated protein kinase were analyzed. X-ray irradiation increased the mRNA expressions of TLR2 and TLR4, and treatment with a protein synthesis inhibitor cycloheximide abolished the radiation-induced upregulation of their cell surface expressions. These results indicate that radiation increased those receptors through de novo protein synthesis. Furthermore, treatment with an antioxidant NAC suppressed not only the radiation-induced upregulation of cell surface expressions of TLR2 and TLR4, but also the radiation-induced activation of the c-Jun N-terminal kinase (JNK) pathway. Since it has been shown that the inhibitor for JNK can suppress the radiation-induced upregulation of TLR expression, the present results suggest that ionizing radiation increased the cell surface expressions of TLR2 and TLR4 through reactive oxygen species–mediated JNK activation.

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Flavonoids, the Family of Plant-derived Antioxidants making inroads into Novel Therapeutic Design against IR-induced Oxidative Stress in Parkinson’s Disease

Current Neuropharmacology ◽

10.2174/1570159x19666210524152817 ◽

2021 ◽

Vol 19 ◽

Author(s):

Tapan Behl ◽

Gagandeep Kaur ◽

Aayush Sehgal ◽

Gokhan Zengin ◽

Sukhbir Singh ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Ionizing Radiation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Radiation Induced ◽

Novel Therapeutic

Background: Ionizing radiation from telluric sources is unceasingly an unprotected pitfall to humans. Thus, the foremost contributors to human exposure are global and medical radiations. Various pieces of evidences assembled during preceding years reveal the pertinent role of ionizing radiation-induced oxidative stress in the progression of neurodegenerative insults such as Parkinson’s disease, which have been contributing to increased proliferation and generation of reactive oxygen species. Objective: This review delineates the role of ionizing radiation-induced oxidative stress in Parkinson’s disease and proposes novel therapeutic interventions of flavonoid family offering effective management and slowing down the progression of Parkinson’s disease. Method: Published papers were searched via MEDLINE, PubMed, etc. published to date for in-depth database collection. Results: The potential of oxidative damage may harm the non-targeted cells. It can also modulate the functions of central nervous system, such as protein misfolding, mitochondria dysfunction, increased levels of oxidized lipids, and dopaminergic cell death, which accelerates the progression of Parkinson’s disease at the molecular, cellular, or tissue levels. In Parkinson’s disease, reactive oxygen species exacerbate the production of nitric oxides and superoxides by activated microglia, rendering death of dopaminergic neuronal cell through different mechanisms. Conclusion: Rising interest has extensively engrossed on the clinical trial designs based on the plant derived family of antioxidants. They are known to exert multifarious impact either way in neuroprotection via directly suppressing ionizing radiation-induced oxidative stress and reactive oxygen species production or indirectly increasing the dopamine levels and activating the glial cells.

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Nuclear Abl Drives miR-34c Transfer by Extracellular Vesicles to Induce Radiation Bystander Effects

10.1101/209767 ◽

2017 ◽

Author(s):

Shubhra Rastogi ◽

Amini Hwang ◽

Josolyn Chan ◽

Jean YJ Wang

Keyword(s):

Reactive Oxygen Species ◽

Dna Damage ◽

Ionizing Radiation ◽

Extracellular Vesicles ◽

Reactive Oxygen ◽

Nuclear Accumulation ◽

Oxygen Species ◽

Bystander Effects ◽

Abl Tyrosine Kinase ◽

Radiation Induced

SUMMARYIonizing radiation stimulates nuclear accumulation of Abl tyrosine kinase that is required for directly irradiated cells to produce microRNA-34c-containing extracellular vesicles, which transfer the microRNA into non-irradiated cells to induce reactive oxygen species and bystander DNA damage.ABSTRACTIonizing radiation (IR) activates an array of DNA damage response (DDR) that includes the induction of bystander effects (BE) in cells not targeted by radiation. How DDR pathways in irradiated cells stimulate BE in non-targeted cells is mostly unknown. We show here that extracellular vesicles from irradiated cells (EV-IR) induce reactive oxygen species (ROS) and DNA damage when internalized by un-irradiated cells. We found that EV-IR from Abl-NLS-mutated cells could not induce ROS or DNA damage, and restoration of nuclear Abl rescued those defects. Expanding a previous finding that Abl stimulates miR-34c expression, we show here that nuclear Abl also drives the vesicular secretion of miR-34c. Ectopic miR-34c expression, without irradiation, generated EV-miR-34c capable of inducing ROS and DNA damage. Furthermore, EV-IR from miR34-knockout cells could not induce ROS and raised γH2AX to lesser extent than EV-IR from miR34-wild type cells. These results establish a novel role for the Abl-miR-34c DDR pathway in stimulating radiation-induced bystander effects.

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Quercetin Prevents Radiation-Induced Oral Mucositis by Upregulating BMI-1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/2231680 ◽

2021 ◽

Vol 2021 ◽

pp. 1-16

Author(s):

Jing Zhang ◽

Yiyang Hong ◽

Zhenyu Liuyang ◽

Haozhe Li ◽

Zhongyang Jiang ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Epithelial Cells ◽

Ionizing Radiation ◽

Oral Mucositis ◽

Proinflammatory Cytokine ◽

Reactive Oxygen Species Generation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Term Survival ◽

Radiation Induced

Radiation-induced oral mucositis is a major adverse event of radiotherapy. Severe oral mucositis may cause unwanted interruption in radiotherapy and reduce long-term survival in cancer patients receiving radiotherapy, but until now, there have been no effective options for preventing radiation-induced oral mucositis. Quercetin is a flavonoid that is widely found in food species and has anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated a new role of quercetin in preventing radiation-induced oral mucositis. Quercetin exerted preventive effects against radiation-induced oral mucositis induced by single-dose (25 Gy) ionizing radiation or fractionated ionizing radiation ( 8 Gy × 3 ) in C57BL/6 mice and maintained the proliferation ability of basal epithelial cells. Quercetin pretreatment alleviated reactive oxygen species generation, NF-κB pathway activation, and downstream proinflammatory cytokine production and reduced DNA double-strand breaks and cellular senescence induced by ionizing radiation. Quercetin also upregulated BMI-1 expression in oral epithelial cells and promoted ulcer repair. In addition, quercetin exerted similar radioprotective effects in irradiated primary cultured normal human keratinocytes, reduced reactive oxygen species generation and proinflammatory cytokine release, and promoted DNA double-strand break repair and wound healing by upregulating the expression of BMI-1, which is a polycomb group protein. Thus, quercetin can block multiple pathological processes of radiation-induced oral mucositis by targeting BMI-1 and may be a potential treatment option for preventing radiation-induced oral mucositis.

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Ionizing radiation-induced micronucleus formation is mediated by reactive oxygen species that are produced in a manner dependent on mitochondria, Nox1, and JNK

Oncology Reports ◽

10.3892/or.17.5.1183 ◽

2007 ◽

Cited By ~ 4

Author(s):

Kyung-Mi Choi ◽

Chang-Mo Kang ◽

Eun Cho ◽

Seong Kang ◽

Seung Lee ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Ionizing Radiation ◽

Reactive Oxygen ◽

Oxygen Species ◽

Micronucleus Formation ◽

Radiation Induced

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1128 Reactive Oxygen Species May Play a Role in Ionizing Radiation-induced Bystander Effects and Regulation of mRNA Levels by MicroRNAs

European Journal of Cancer ◽

10.1016/s0959-8049(12)71729-x ◽

2012 ◽

Vol 48 ◽

pp. S271-S272 ◽

Cited By ~ 1

Author(s):

J. Rzeszowska-Wolny ◽

M. Widel ◽

A. Cieslar-Pobuda ◽

A. Lalik ◽

M. Skonieczna ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Ionizing Radiation ◽

Reactive Oxygen ◽

Mrna Levels ◽

Oxygen Species ◽

Bystander Effects ◽

Radiation Induced

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ROS responsive EPO nanoparticle ameliorates ionizing radiation-induced hematopoietic injury

Biomaterials Science ◽

10.1039/d1bm00919b ◽

2021 ◽

Author(s):

Huiyang Li ◽

Xiaoyu Liang ◽

Jianwei Duan ◽

Youlu Chen ◽

Xinxin Tian ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Ionizing Radiation ◽

Active Site ◽

Drug Carrier ◽

Reactive Oxygen ◽

Polymer Materials ◽

Oxygen Species ◽

Stimulus Responsive ◽

Responsive Polymer ◽

Radiation Induced

Stimulus-responsive polymer materials have attracted much attention as drug carrier because of the ability to deliver drug to the active site. Reactive oxygen species (ROS) plays crucial roles in cellular...

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