scholarly journals Role of Oxidative RNA Damage in Chronic-Degenerative Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Carmela Fimognari
Keyword(s):  
Oxidative Damage ◽  
Cell Damage ◽  
Rna Degradation ◽  
Degenerative Diseases ◽  
Aberrant Expression ◽  
Toxic Agents ◽  
Its Gene ◽  
Rna Damage ◽  
Exogenous Agents

Normal cellular metabolism and exposure to ionizing and ultraviolet radiations and exogenous agents produce reactive oxygen species (ROS). Due to their reactivity, they can interact with many critical biomolecules and induce cell damage. The reaction of ROS with free nucleobases, nucleosides, nucleotides, or oligonucleotides can generate numerous distinct modifications in nucleic acids. Oxidative damage to DNA has been widely investigated and is strongly implicated in the development of many chronic-degenerative diseases. In contrast, RNA damage is a poorly examined field in biomedical research. In this review, I discuss the importance of RNA as a target of oxidative damage and the role of oxidative damage to RNA in the pathogenesis of some chronic-degenerative diseases, such as neurological disorders, atherosclerosis, and cancer. Furthermore, I review recent evidence suggesting that RNA may be the target for toxic agents and indicating RNA degradation as a powerful tool to treat any pathology in which there is an aberrant expression of mRNA and/or its gene products.

scholarly journals The Role of Thioredoxin/Peroxiredoxin in the β-Cell Defense Against Oxidative Damage

2021 ◽  
Vol 12 ◽  
Author(s):  
Jennifer S. Stancill ◽  
John A. Corbett
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Cell Function ◽  
Cell Damage ◽  
Thioredoxin Reductase ◽  
Β Cells ◽  
Β Cell ◽  
Cell Defense ◽  
Β Cell Function

Oxidative stress is hypothesized to play a role in pancreatic β-cell damage, potentially contributing to β-cell dysfunction and death in both type 1 and type 2 diabetes. Oxidative stress arises when naturally occurring reactive oxygen species (ROS) are produced at levels that overwhelm the antioxidant capacity of the cell. ROS, including superoxide and hydrogen peroxide, are primarily produced by electron leak during mitochondrial oxidative metabolism. Additionally, peroxynitrite, an oxidant generated by the reaction of superoxide and nitric oxide, may also cause β-cell damage during autoimmune destruction of these cells. β-cells are thought to be susceptible to oxidative damage based on reports that they express low levels of antioxidant enzymes compared to other tissues. Furthermore, markers of oxidative damage are observed in islets from diabetic rodent models and human patients. However, recent studies have demonstrated high expression of various isoforms of peroxiredoxins, thioredoxin, and thioredoxin reductase in β-cells and have provided experimental evidence supporting a role for these enzymes in promoting β-cell function and survival in response to a variety of oxidative stressors. This mini-review will focus on the mechanism by which thioredoxins and peroxiredoxins detoxify ROS and on the protective roles of these enzymes in β-cells. Additionally, we speculate about the role of this antioxidant system in promoting insulin secretion.

MicroRNAs in Noise-Induced Hearing Loss and their Regulation by Oxidative Stress and Inflammation

2020 ◽  
Vol 21 (12) ◽  
pp. 1216-1224
Author(s):  
Fatemeh Forouzanfar ◽  
Samira Asgharzade
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Hair Cell ◽  
Noise Exposure ◽  
Cell Damage ◽  
Sensory Cells ◽  
Noise Induced Hearing Loss ◽  
Irreversible Damage ◽  
Open Access Journals

Noise exposure (NE) has been recognized as one of the causes of sensorineural hearing loss (SNHL), which can bring about irreversible damage to sensory hair cells in the cochlea, through the launch of oxidative stress pathways and inflammation. Accordingly, determining the molecular mechanism involved in regulating hair cell apoptosis via NE is essential to prevent hair cell damage. However, the role of microRNAs (miRNAs) in the degeneration of sensory cells of the cochlea during NE has not been so far uncovered. Thus, the main purpose of this study was to demonstrate the regulatory role of miRNAs in the oxidative stress pathway and inflammation induced by NE. In this respect, articles related to noise-induced hearing loss (NIHL), oxidative stress, inflammation, and miRNA from various databases of Directory of Open Access Journals (DOAJ), Google Scholar, PubMed; Library, Information Science & Technology Abstracts (LISTA), and Web of Science were searched and retrieved. The findings revealed that several studies had suggested that up-regulation of miR-1229-5p, miR-451a, 185-5p, 186 and down-regulation of miRNA-96/182/183 and miR-30b were involved in oxidative stress and inflammation which could be used as biomarkers for NIHL. There was also a close relationship between NIHL and miRNAs, but further research is required to prove a causal association between miRNA alterations and NE, and also to determine miRNAs as biomarkers indicating responses to NE.

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.

ZFARED: A Database of the Antioxidant Response Elements in Zebrafish

2020 ◽  
Vol 15 (5) ◽  
pp. 415-419
Author(s):  
Azhwar Raghunath ◽  
Raju Nagarajan ◽  
Ekambaram Perumal
Keyword(s):  
Target Genes ◽  
Antioxidant Response ◽  
Zebrafish Genome ◽  
Promoter Regions ◽  
Protein Coding ◽  
Response Elements ◽  
Toxic Agents ◽  
Upstream Promoter ◽  
Its Gene ◽  
Antioxidant Response Elements

Background: Antioxidant Response Elements (ARE) play a key role in the expression of Nrf2 target genes by regulating the Keap1-Nrf2-ARE pathway, which offers protection against toxic agents and oxidative stress-induced diseases. Objective: To develop a database of putative AREs for all the genes in the zebrafish genome. This database will be helpful for researchers to investigate Nrf2 regulatory mechanisms in detail. Methods: To facilitate researchers functionally characterize zebrafish AREs, we have developed a database of AREs, Zebrafish Antioxidant Response Element Database (ZFARED), for all the protein-coding genes including antioxidant and mitochondrial genes in the zebrafish genome. The front end of the database was developed using HTML, JavaScript, and CSS and tested in different browsers. The back end of the database was developed using Perl scripts and Perl-CGI and Perl- DBI modules. Results: ZFARED is the first database on the AREs in zebrafish, which facilitates fast and efficient searching of AREs. AREs were identified using the in-house developed Perl algorithms and the database was developed using HTML, JavaScript, and Perl-CGI scripts. From this database, researchers can access the AREs based on chromosome number (1 to 25 and M for mitochondria), strand (positive or negative), ARE pattern and keywords. Users can also specify the size of the upstream/promoter regions (5 to 30 kb) from transcription start site to access the AREs located in those specific regions. Conclusion: ZFARED will be useful in the investigation of the Keap1-Nrf2-ARE pathway and its gene regulation. ZFARED is freely available at http://zfared.buc.edu.in/.

Mechanisms of Nickel-Induced Cell Damage in Allergic Contact Dermatitis and Nutritional Intervention Strategies

2020 ◽  
Vol 20 (7) ◽  
pp. 1010-1014 ◽  
Author(s):  
Dana Filatova ◽  
Christine Cherpak
Keyword(s):  
Lipid Peroxidation ◽  
Contact Dermatitis ◽  
Oxidative Damage ◽  
Allergic Contact Dermatitis ◽  
Cell Damage ◽  
Consumer Products ◽  
The Body ◽  
Cellular Damage ◽  
Nutritional Interventions ◽  
Allergic Contact

Background: Hypersensitivity to nickel is a very common cause of allergic contact dermatitis since this metal is largely present in industrial and consumer products as well as in some commonly consumed foods, air, soil, and water. In nickel-sensitized individuals, a cell-mediated delayed hypersensitivity response results in contact to dermatitis due to mucous membranes coming in long-term contact with nickel-containing objects. This process involves the generation of reactive oxidative species and lipid peroxidation-induced oxidative damage. Immunologically, the involvement of T helper (h)-1 and Th-2 cells, as well as the reduced function of T regulatory cells, are of importance. The toxicity, mutagenicity, and carcinogenicity of nickel are attributed to the generation of reactive oxygen species and induction of oxidative damage via lipid peroxidation, which results in DNA damage. Objective: The aim of this research is to identify nutritionally actionable interventions that can intercept nickel-induced cell damage due to their antioxidant capacities. Conclusion: Nutritional interventions may be used to modulate immune dysregulation, thereby intercepting nickel-induced cellular damage. Among these nutritional interventions are a low-nickel diet and an antioxidant-rich diet that is sufficient in iron needed to minimize nickel absorption. These dietary approaches not only reduce the likelihood of nickel toxicity by minimizing nickel exposure but also help prevent oxidative damage by supplying the body with antioxidants that neutralize free radicals.

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

scholarly journals Moonlighting in Bacillus subtilis: The Small Proteins SR1P and SR7P Regulate the Moonlighting Activity of Glyceraldehyde 3-Phosphate Dehydrogenase A (GapA) and Enolase in RNA Degradation

2021 ◽  
Vol 9 (5) ◽  
pp. 1046
Author(s):  
Inam Ul Haq ◽  
Sabine Brantl
Keyword(s):  
Bacillus Subtilis ◽  
Antisense Rna ◽  
Rna Binding ◽  
Rna Degradation ◽  
Metabolic Enzyme ◽  
Dual Function ◽  
Small Proteins ◽  
Moonlighting Proteins ◽  
Rnase Y

Moonlighting proteins are proteins with more than one function. During the past 25 years, they have been found to be rather widespread in bacteria. In Bacillus subtilis, moonlighting has been disclosed to occur via DNA, protein or RNA binding or protein phosphorylation. In addition, two metabolic enzymes, enolase and phosphofructokinase, were localized in the degradosome-like network (DLN) where they were thought to be scaffolding components. The DLN comprises the major endoribonuclease RNase Y, 3′-5′ exoribonuclease PnpA, endo/5′-3′ exoribonucleases J1/J2 and helicase CshA. We have ascertained that the metabolic enzyme GapA is an additional component of the DLN. In addition, we identified two small proteins that bind scaffolding components of the degradosome: SR1P encoded by the dual-function sRNA SR1 binds GapA, promotes the GapA-RNase J1 interaction and increases the RNase J1 activity. SR7P encoded by the dual-function antisense RNA SR7 binds to enolase thereby enhancing the enzymatic activity of enolase bound RNase Y. We discuss the role of small proteins in modulating the activity of two moonlighting proteins.

scholarly journals Cancer Stem Cells Are Possible Key Players in Regulating Anti-Tumor Immune Responses: The Role of Immunomodulating Molecules and MicroRNAs

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1674
Author(s):  
Sara Tomei ◽  
Ola Ibnaof ◽  
Shilpa Ravindran ◽  
Soldano Ferrone ◽  
Cristina Maccalli
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Immune Responses ◽  
Antigen Processing ◽  
Aberrant Expression ◽  
Immunological Profile ◽  
Malignant Lesions ◽  
Novel Therapeutic Strategies ◽  
Antigen Processing And Presentation

Cancer cells endowed with stemness properties and representing a rare population of cells within malignant lesions have been isolated from tumors with different histological origins. These cells, denominated as cancer stem cells (CSCs) or cancer initiating cells (CICs), are responsible for tumor initiation, progression and resistance to therapies, including immunotherapy. The dynamic crosstalk of CSCs/CICs with the tumor microenvironment orchestrates their fate and plasticity as well as their immunogenicity. CSCs/CICs, as observed in multiple studies, display either the aberrant expression of immunomodulatory molecules or suboptimal levels of molecules involved in antigen processing and presentation, leading to immune evasion. MicroRNAs (miRNAs) that can regulate either stemness properties or their immunological profile, with in some cases dual functions, can provide insights into these mechanisms and possible interventions to develop novel therapeutic strategies targeting CSCs/CICs and reverting their immunogenicity. In this review, we provide an overview of the immunoregulatory features of CSCs/CICs including miRNA profiles involved in the regulation of the interplay between stemness and immunological properties.

scholarly journals KLF7/VPS35 axis contributes to hepatocellular carcinoma progression through CCDC85C-activated β-catenin pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yarong Guo ◽  
Bao Chai ◽  
Junmei Jia ◽  
Mudan Yang ◽  
Yanjun Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Tumor Growth ◽  
Luciferase Reporter ◽  
Aberrant Expression ◽  
Proliferation And Invasion ◽  
Hcc Cells

Abstract Objective Dysregulation of KLF7 participates in the development of various cancers, but it is unclear whether there is a link between HCC and aberrant expression of KLF7. The aim of this study was to investigate the role of KLF7 in proliferation and migration of hepatocellular carcinoma (HCC) cells. Methods CCK8, colony growth, transwell, cell cycle analysis and apoptosis detection were performed to explore the effect of KLF7, VPS35 and Ccdc85c on cell function in vitro. Xenografted tumor growth was used to assess in vivo role of KLF7. Chip-qPCR and luciferase reporter assays were applied to check whether KLF7 regulated VPS35 at transcriptional manner. Co-IP assay was performed to detect the interaction between VPS35 and Ccdc85c. Immunohistochemical staining and qRT-PCR analysis were performed in human HCC sampels to study the clinical significance of KLF7, VPS35 and β-catenin. Results Firstly, KLF7 was highly expressed in human HCC samples and correlated with patients’ differentiation and metastasis status. KLF7 overexpression contributed to cell proliferation and invasion of HCC cells in vitro and in vivo. KLF7 transcriptional activation of VPS35 was necessary for HCC tumor growth and metastasis. Further, co-IP studies revealed that VPS35 could interact with Ccdc85c in HCC cells. Rescue assay confirmed that overexpression of VPS35 and knockdown of Ccdc85c abolished the VPS35-medicated promotion effect on cell proliferation and invasion. Finally, KLF7/VPS35 axis regulated Ccdc85c, which involved in activation of β-catenin signaling pathway, confirmed using β-catenin inhibitor, GK974. Functional studies suggested that downregulation of Ccdc85c partly reversed the capacity of cell proliferation and invasion in HCC cells, which was regulated by VPS35 upregulation. Lastly, there was a positive correlation among KLF7, VPS35 and active-β-catenin in human HCC patients. Conclusion We demonstrated that KLF7/VPS35 axis promoted HCC cell progression by activating Ccdc85c-medicated β-catenin pathway. Targeting this signal axis might be a potential treatment strategy for HCC.

scholarly journals Selectivity of mRNA degradation by autophagy in yeast

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shiho Makino ◽  
Tomoko Kawamata ◽  
Shintaro Iwasaki ◽  
Yoshinori Ohsumi
Keyword(s):  
Ribosomal Proteins ◽  
Rna Degradation ◽  
Mrna Degradation ◽  
Ribosome Profiling ◽  
Genome Wide ◽  
Tightly Coupled ◽  
Response To Stress ◽  
Transcriptional Gene Regulation ◽  
Synthesis And Degradation

AbstractSynthesis and degradation of cellular constituents must be balanced to maintain cellular homeostasis, especially during adaptation to environmental stress. The role of autophagy in the degradation of proteins and organelles is well-characterized. However, autophagy-mediated RNA degradation in response to stress and the potential preference of specific RNAs to undergo autophagy-mediated degradation have not been examined. In this study, we demonstrate selective mRNA degradation by rapamycin-induced autophagy in yeast. Profiling of mRNAs from the vacuole reveals that subsets of mRNAs, such as those encoding amino acid biosynthesis and ribosomal proteins, are preferentially delivered to the vacuole by autophagy for degradation. We also reveal that autophagy-mediated mRNA degradation is tightly coupled with translation by ribosomes. Genome-wide ribosome profiling suggested a high correspondence between ribosome association and targeting to the vacuole. We propose that autophagy-mediated mRNA degradation is a unique and previously-unappreciated function of autophagy that affords post-transcriptional gene regulation.

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