Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8IXL6 (RNS)
 1,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Radiotherapy-induced toxicity is a major dose-limiting factor in anti-cancer treatment. Ionizing radiation leads to the formation of reactive oxygen and nitrogen species (ROS/RNS) that are associated with radiation-induced cell death. Investigations of biological effects of fullerenol have provided evidence for its ROS/RNS scavenger properties in vitro and radioprotective efficiency in vivo. Therefore we were interested to evaluate its radioprotective properties in vitro in the human erythroleukemia cell line. Pre-treatment of irradiated cells by fullerenol exerted statistically significant effects on cell numbers and the response of antioxidative enzymes to X-ray irradiation-induced oxidative stress in cells. Our study provides evidence that the pre-treatment with fullerenol enhanced the enzymatic activity of superoxide dismutase and glutathione peroxidase in irradiated K562 cells.
 ...
PMID:Fullerenol C60(OH)24 effects on antioxidative enzymes activity in irradiated human erythroleukemia cell line. 1828 60

Reactive oxygen and nitrogen species (ROS and RNS) are known to contribute as pathogenic factors to the development of chronic progressive diseases at various stages. The present review discusses the role of oxidative stress in chemically induced cancer development and progression. Reactive species are capable of inducing DNA damage that eventually may contribute to cell transformation and tumor initiation. ROS and RNS are also associated with tumor promotion and progression. Both endogenous processes and redox-cycling of xenobiotic compounds have been shown to result in oxidative DNA damage. In addition, several exocyclic DNA adducts represent secondary DNA damage caused by products of lipid peroxidation in the course of oxidative cellular stress. Due to their intrinsic ability to catalyze redox reactions, transition metals, and quinones from various classes of xenobiotics or endogenous compounds are important mediators of oxidative stress and thus likely of being involved in DNA damage, lipid peroxidation, cell transformation, and tumor development.
Cancer Lett 2008 Jul 18
PMID:Reactive species: a cell damaging rout assisting to chemical carcinogens. 1836 25

Environmental and occupational toxicants may induce pulmonary inflammation. Chronic inflammation has been linked to several human diseases and also to initiation and promotion of cancer. Generation of reactive oxygen/nitrogen species (ROS/RNS), secretion of cytokines, chemokines and pro-angiogenic factors are believed to play a role. Interleukin IL-1beta, encoded by the IL1B gene, is a key cytokine produced and secreted by many cell types after activation by biological or chemical agents. Several polymorphisms in the IL1B gene have been identified, and some are associated with increased risk for lung cancer. Especially, the IL1B -31T/C polymorphism has received attention. We have investigated the effect of the lung carcinogens cigarette-smoke condensate (CSC) and benzo[a]pyrene (B[a]P) on the promoters of the IL1B gene varying only at the site of the -31T/C polymorphism. The promoter fragments containing either C or T were cloned in luciferase reporter vectors and transfected into human lung epithelial NCI-H2009 cells. The results show that treatment of the transfected cells with CSC or B[a]P induced the promoter significantly above the control level. Interestingly, the promoter with the wild-type allele T in position -31 showed the stronger induction when compared with the promoter with variant allele C in this position. Bioinformatics and DNA-protein analysis indicated the presence of a novel transcription-factor binding site and the formation of protein complexes at the C promoter.
 ...
PMID:Allele-specific induction of IL1B -31T/C promoter polymorphism by lung carcinogens. 1865 50

Redox balance is particularly important in the airways because they are the first points of contact with environmental pollutants such as ozone, particles, and cigarette smoke, as well as pathogens such as bacteria and viruses. However, an imbalance between toxicant-induced reactive oxygen (ROS) and nitrogen (RNS) species and the antioxidant defense system leads to oxidative stress, which has been implicated in the development and/or perpetuation of airway diseases, including malignancy. Various antioxidant enzymes and proteins are critical to maintaining the reducing environment of the cell and preventing the damage to various biomolecules that is elicited by ROS/RNS. Emerging evidence indicates that transcriptional activation of the antioxidant response element (ARE) plays a crucial role in modulating oxidative stress and providing cytoprotection against prooxidant stimuli. This review focuses on the regulation and functional roles of key effectors that bind to the ARE and differentially (up- or down-) regulate gene expression in lung tissue/cell types in response to respiratory toxicants. It also provides a perspective on whether boosting ARE-mediated gene expression with dietary plants and synthetic plant products will offer a better therapeutic strategy for mitigating oxidative stress and respiratory pathogenesis.
 ...
PMID:The antioxidant response element and oxidative stress modifiers in airway diseases. 1869 Oct 64

Oxidative stress is a "privilege" of aerobic organisms. It can be induced by endogenous and exogenous factors. Most often, it is characterized by the production of free radicals and nonradical oxygen and nitrogen products, referred to under a single term "reactive species" (RS). Oxidative stress is a deleterious process that can be an important mediator of damage to cell structures, including lipids and membranes, proteins and DNA. However, reactive oxygen (ROS) and nitrogen species (RNS) are "two-faced" products. Produced in low/moderate concentrations as molecular signals that regulate a series of physiological processes, such as a defence against infectious agents, the maintenance of vascular tone, the control of ventilation and erythropoietin production, and signal transduction from membrane receptors in various physiological processes. Many of ROS-mediated responses protect cells against oxidative stress and maintain "redox homeostasis". Then, both reactive species are produced by strictly regulated enzymes, such as nitric oxide synthase (NOS), and isoforms of NADPH oxidase, or as by-products from not so well regulated sources, such as the mitochondrial electron-transport chain. An excessive increase in ROS production has been implicated in the pathogenesis of atherosclerosis, cardiovascular diseases, hypertension, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative and immuno-inflammatory diseases. Within the cells, ROS can act as secondary messengers in intracellular signalling cascades, which can induce the oncogenic phenotype of cancer cells, cellular senescence and apoptosis.
 ...
PMID:[Oxidative stress in human diseases]. 1892 87

MnTE-2-PyP(5+) is a potent catalytic scavenger of reactive oxygen and nitrogen species, primarily superoxide and peroxynitrite. It therefore not only attenuates primary oxidative damage, but was found to modulate redox-based signaling pathways (HIF-1alpha, NF-kappaB, SP-1, and AP-1) and thus, in turn, secondary oxidative injury also. Cancer has been widely considered an oxidative stress condition. The goal of this study was to prove if and why a catalytic SOD mimic/peroxynitrite scavenger would exert anti-cancer effects, i.e., to evaluate whether the attenuation of the oxidative stress by MnTE-2-PyP(5+) could suppress tumor growth in a 4T1 mouse breast tumor model. Tumor cells were implanted into Balb/C mouse flanks. Three groups of mice (n=25) were studied: control (PBS) and 2 and 15 mg/kg/day of MnTE-2-PyP(5+) given subcutaneously twice daily starting when the tumors averaged 200 mm(3) (until they reached approximately 5-fold the initial volume). Intratumoral hypoxia (pimonidazole, carbonic anhydrase), HIF-1alpha, VEGF, proliferating capillary index (CD105), microvessel density (CD31), protein nitration, DNA oxidation (8-OHdG), NADPH oxidase (Nox-4), apoptosis (CD31), macrophage infiltration (CD68), and tumor drug levels were assessed. With 2 mg/kg/day a trend toward tumor growth delay was observed, and a significant trend was observed with 15 mg/kg/day. The 7.5-fold increase in drug dose was accompanied by a similar (6-fold) increase in tumor drug levels. Oxidative stress was largely attenuated as observed through the decreased levels of DNA damage, protein 3-nitrotyrosine, macrophage infiltration, and NADPH oxidase. Further, hypoxia was significantly decreased as were the levels of HIF-1alpha and VEGF. Consequently, suppression of angiogenesis was observed; both the microvessel density and the endothelial cell proliferation were markedly decreased. Our study indicates for the first time that MnTE-2-PyP(5+) has anti-cancer activity in its own right. The anti-cancer activity via HIF/VEGF pathways probably arises from the impact of the drug on the oxidative stress. Therefore, the catalytic scavenging of ROS/RNS by antioxidants, which in turn suppresses cellular transcriptional activity, could be an appropriate strategy for anti-cancer therapy. Enhancement of the anti-cancer effects may be achieved by optimizing the dosing regime, utilizing more bioavailable Mn porphyrins (MnP), and combining MnP treatment with irradiation, hyperthermia, and chemotherapy. Mn porphyrins may be advantageous compared to other anti-cancer drugs, owing to their radioprotection of normal tissue and the ability to afford pain management in cancer patients via prevention of chronic morphine tolerance.
 ...
PMID:Antiangiogenic action of redox-modulating Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin, MnTE-2-PyP(5+), via suppression of oxidative stress in a mouse model of breast tumor. 1959 20

Although the mitochondrial permeability transition pore (mPTP) was first discovered almost 30 years ago [1], it did not attract significant research attention until the 1990's when several studies implicated mPTP in apoptosis [2]. Today, the dogma suggests that opening of mPTP is detrimental to the cell and mPTP activation is widely thought to contribute to disease in cancer, neurodegenerative diseases, stroke, muscular dystrophy, and cardiac reperfusion injury [3]. Multiple factors including Ca(2+), OH(-), P(i), cyclophilin D, reactive oxygen and nitrogen species (ROS and RNS) trigger mPTP opening [4]. However, whether mPTP activation feeds back to alter mitochondrial ROS generation remains unclear. We recently demonstrated that under normal conditions, individual mitochondria undergo spontaneous transient bursts of quantal superoxide generation, termed "superoxide flashes" [5]. Superoxide flashes are observed in all cell types investigated to date and are triggered by a surprising functional coupling between mPTP activation and electron transport chain (ETC) dependent superoxide production. Additionally, reoxgenation following anoxia leads to uncontrolled superoxide flash genesis in cardiomyocytes. This positive feedback mechanism for mPTP/ETC-dependent ROS generation may drive localized redox signaling in individual mitochondria under physiological conditions, and when left unchecked, contribute to global cellular oxidative stress under pathological conditions in cardiac disease. The mPTP activity-dependent cell life and death determination imposes new challenges and opportunities in the pursuit of therapeutic agents for treating diseases in which oxidative stress has been implicated such as cardiac ischemia-reperfusion injury.
 ...
PMID:Superoxide flashes: illuminating new insights into cardiac ischemia/reperfusion injury. 1964 73

Free radicals derived from oxygen, nitrogen and sulphur molecules in the biological system are highly active to react with other molecules due to their unpaired electrons. These radicals are important part of groups of molecules called reactive oxygen/nitrogen species (ROS/RNS), which are produced during cellular metabolism and functional activities and have important roles in cell signalling, apoptosis, gene expression and ion transportation. However, excessive ROS attack bases in nucleic acids, amino acid side chains in proteins and double bonds in unsaturated fatty acids, and cause oxidative stress, which can damage DNA, RNA, proteins and lipids resulting in an increased risk for cardiovascular disease, cancer, autism and other diseases. Intracellular antioxidant enzymes and intake of dietary antioxidants may help to maintain an adequate antioxidant status in the body. In the past decades, new molecular techniques, cell cultures and animal models have been established to study the effects and mechanisms of antioxidants on ROS. The chemical and molecular approaches have been used to study the mechanism and kinetics of antioxidants and to identify new potent antioxidants. Antioxidants can decrease the oxidative damage directly via reacting with free radicals or indirectly by inhibiting the activity or expression of free radical generating enzymes or enhancing the activity or expression of intracellular antioxidant enzymes. The new chemical and cell-free biological system has been applied in dissecting the molecular action of antioxidants. This review focuses on the research approaches that have been used to study oxidative stress and antioxidants in lipid peroxidation, DNA damage, protein modification as well as enzyme activity, with emphasis on the chemical and cell-free biological system.
 ...
PMID:Chemical and molecular mechanisms of antioxidants: experimental approaches and model systems. 1975 73

Saliva testing, a non-invasive alternative to serum testing, may be an effective modality for diagnosis and for prognosis prediction of oral cancer, as well as for monitoring post therapy status, by measuring specific salivary macromolecules, examining proteomic or genomic targets such as enzymes, cytokines, growth factors, metalloproteinases, endothelin, telomerase, cytokeratines, mRNA's and DNA transcripts. Salivary analysis has been shown to be a useful diagnostic tool also for distant malignancies such as breast cancer. In recent years, significant alterations have been demonstrated in the saliva of oral cancer patients in the epithelial tumor markers--Cyfra 21-1, TPS and CA12, various oxidative stress-related salivary parameters as ROS and RNS, biochemical and immunological parameters as IGF and MMP's and RNA transcripts of IL8, IL-1B, DUSP1, HA3, OAZ1, S100P, and SAT. Collectively these accumulated data are predicted to alter the field of oral cancer diagnosis by employing highly sensitive new tools which will enable both medical professionals and the patients themselves to monitor their saliva for diagnosis and prognosis prediction, as they relate to oral cancer. At this point however, the aim of salivary analysis is mainly for screening which may be helpful in the future.
 ...
PMID:Saliva as a tool for oral cancer diagnosis and prognosis. 1982 59

For many years the formation of reactive oxygen and nitrogen species (ROS) and (RNS) in living organisms has been considered to be dangerous phenomenon due to their damaging action on biomolecules. However, present studies demonstrated another important activity of ROS and RNS: their signaling functions in physiological and pathological processes. In this work we discuss the new data concerning a role of ROS and RNS in many enzymatic/gene cascades causing damaging changes during the development of skin diseases and pathological disorders (skin cancer, the toxic effects of irradiation on the skin, and skin wounding). It has been suggested that the enhancement of ROS formation in tumor cells through the inactivation of mitochondrial MnSOD or the activation of NADPH oxidase leads to apoptosis and might be applied for developing a new cancer therapy. On the other hand ROS overproduction might stimulate malignant transformation of melanoma. Role of ROS signaling is also considered in the damaging action of UVA, UVB, and IRA irradiation on the skin and the processes of wound healing. In the last part of review the possibility of the right choice of antioxidants and free radical scavengers for the treatment of skin disease is discussed.
 ...
PMID:Signaling by reactive oxygen and nitrogen species in skin diseases. 2054 Jun 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>