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

Increasing evidence suggests that oxidative and nitrosative stress play an important role in regulation of cardiac myocyte growth and survival. The cardiovascular system is continuously exposed to both reactive oxygen species (ROS) and nitrogen species (RNS), collectively termed reactive inflammatory species (RIS), and imbalances between the enzymes that regulate their bioavailability are associated with cardiac hypertrophy and the pathogenesis of cardiomyopathies, myocardial infarction and heart failure. It is now clear that RIS act as critical regulators of cardiac myocyte hypertrophy and apoptosis through control of redox-sensitive signaling cascades, such as tyrosine kinases and phosphatases, protein kinase C, and mitogen-activated protein kinases. This review will focus on the mechanisms by which ROS/RNS modulate cardiac myocyte growth and apoptosis induced by neurohormones and cytokines, and will discuss evidence for a role in the pathophysiology of heart failure.
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PMID:Regulation of hypertrophic and apoptotic signaling pathways by reactive oxygen species in cardiac myocytes. 1458 46

Dysregulation of the myocardial extracellular matrix contributes to abnormal cardiac muscle function. Changes in the balance between matrix deposition and matrix degradation by matrix metalloproteinases (MMPs) can lead to cardiac fibrosis and dilation. In this review, we discuss the regulation of MMPs, their endogenous inhibitors (TIMPs) and collagen synthesis by inflammatory cytokines and reactive oxygen/nitrogen species (ROS/RNS). Inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, and ROS activate mitogen-activated protein kinases and stress-responsive protein kinases in cardiac cells. In non-cardiac tissues, inflammatory cytokine activation of these kinases is redox sensitive, suggesting ROS may also be involved in cytokine signaling in the heart. Subsequent activation of transcription factors including AP-1, Ets, and nuclear factor kappa-B leads to increased transcription of MMPs. ROS also directly activate MMPs post-translationally. In addition, inflammatory cytokines and ROS lead to decreased TIMP levels and collagen synthesis. Work in animal models suggests that inhibition of inflammatory cytokine or ROS signaling leads to less myocardial remodeling. Further study of the signaling of regulation of the cardiac extracellular matrix may lead to new approaches for the treatment of myocardial remodeling and failure.
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PMID:Regulation of matrix metalloproteinases by cytokines and reactive oxygen/nitrogen species in the myocardium. 1473 67

Reactive oxygen or nitrogen species (ROS/RNS) generated endogenously or in response to environmental stress have long been implicated in tissue injury in the context of a variety of disease states. ROS/RNS can cause cell death by nonphysiological (necrotic) or regulated pathways (apoptotic). The mechanisms by which ROS/RNS cause or regulate apoptosis typically include receptor activation, caspase activation, Bcl-2 family proteins, and mitochondrial dysfunction. Various protein kinase activities, including mitogen-activated protein kinases, protein kinases-B/C, inhibitor-of-I-kappaB kinases, and their corresponding phosphatases modulate the apoptotic program depending on cellular context. Recently, lipid-derived mediators have emerged as potential intermediates in the apoptosis pathway triggered by oxidants. Cell death mechanisms have been studied across a broad spectrum of models of oxidative stress, including H2O2, nitric oxide and derivatives, endotoxin-induced inflammation, photodynamic therapy, ultraviolet-A and ionizing radiations, and cigarette smoke. Additionally ROS generated in the lung and other organs as the result of high oxygen therapy or ischemia/reperfusion can stimulate cell death pathways associated with tissue damage. Cells have evolved numerous survival pathways to counter proapoptotic stimuli, which include activation of stress-related protein responses. Among these, the heme oxygenase-1/carbon monoxide system has emerged as a major intracellular antiapoptotic mechanism.
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PMID:Mechanisms of cell death in oxidative stress. 1711 87

Inflammation plays a critical role in promoting smooth muscle migration and proliferation during vascular diseases such as postangioplasty restenosis and atherosclerosis. Another common feature of many vascular diseases is the contribution of reactive oxygen (ROS) and reactive nitrogen (RNS) species to vascular injury. Primary sources of ROS and RNS in smooth muscle are several isoforms of NADPH oxidase (Nox) and the cytokine-regulated inducible nitric oxide (NO) synthase (iNOS). One important example of the interaction between NO and ROS is the reaction of NO with superoxide to yield peroxynitrite, which may contribute to the pathogenesis of hypertension. In this review, we discuss the literature that supports an alternate possibility: Nox-derived ROS modulate NO bioavailability by altering the expression of iNOS. We highlight data showing coexpression of iNOS and Nox in vascular smooth muscle demonstrating the functional consequences of iNOS and Nox during vascular injury. We describe the relevant literature demonstrating that the mitogen-activated protein kinases are important modulators of proinflammatory cytokine-dependent expression of iNOS. A central hypothesis discussed is that ROS-dependent regulation of the serine/threonine kinase protein kinase Cdelta is essential to understanding how Nox may regulate signaling pathways leading to iNOS expression. Overall, the integration of nonphagocytic NADPH oxidase with cytokine signaling in general and in vascular smooth muscle in particular is poorly understood and merits further investigation.
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PMID:Regulation of smooth muscle by inducible nitric oxide synthase and NADPH oxidase in vascular proliferative diseases. 1821 30

The present study has been designed and carried out to investigate the protective role of taurine (2-aminoethanesulphonic acid) against NaAsO(2) induced nephrotoxicity. Oral administration of arsenic increased the productions of ROS and RNS, enhanced lipid peroxidation, protein carbonylation and decreased intracellular antioxidant defence in the kidney tissue. Investigating the responsible signalling cascades, it was found that NaAsO(2) administration activates mitogen-activated protein kinases (MAPKs) and NF-kappaB in oxidative stress mediated renal dysfunction and induced apoptotic cell death by the reciprocal regulation of Bcl-2/Bad in association with reducing mitochondrial membrane potential and increased cytosolic cytochrome C as well. Treatment with taurine prior to arsenic administration effectively ameliorated As-induced oxidative renal dysfunctions and apoptotic cell death. Histological studies also support the experimental findings. Combining, results suggest that taurine possesses the ability to ameliorate arsenic-induced oxidative insult and renal damage, probably due to its antioxidant activity and functioning via MAPKs/NF-kappaB and mitochondria dependent pathways.
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PMID:Prophylactic role of taurine on arsenic mediated oxidative renal dysfunction via MAPKs/ NF-kappaB and mitochondria dependent pathways. 1967 40

Dietary flavonoids are a large family of polyphenols ubiquitously expressed in plants. Recent evidence show that flavonoids possess several anti-inflammatory activities due to their ability to scavenge reactive oxygen and nitrogen species (ROS and RNS), to inhibit the pro-inflammatory activity of ROS-generating enzymes including cyclooxygenase (COX), lipoxygenase (LOX) and inducible nitric oxide synthase (iNOS) and to modulate different intracellular signaling pathways from NF-kB to mitogen-activated protein kinases (MAPKs) through perturbation of redox-sensible networks in immune cells. This report will review current knowledge on the anti-inflammatory effects of flavonoids on immune cells focusing on their ability to modulate multiple redox-sensible pathways involved in inflammation.
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PMID:The effects of dietary flavonoids on the regulation of redox inflammatory networks. 2265 88

2-Chloroethyl ethyl sulfide (CEES) is a well-known chemical warfare agent that induces cellular stress in exposed individuals. However, molecular mechanisms of CEES-induced oxidative stress-mediated metabolic deregulation are not clearly elucidated. Here we investigated CEES-induced free radical production act as key functional mediators of metabolic stress via Erk1/2 mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K/Akt) signaling cascades in keratinocytes. We observed that CEES exposure disrupts the cellular antioxidant defense capacities leading to increase in free oxygen and nitrogen radical accumulation in keratinocytes. These unusual cellular abnormalities initiate cellular stress via Erk1/2-PI3K/Akt signaling pathways. Biochemical tools were used to analyze the changes in metabolites including sulfur amino acids (SAAs), namely, L-glutathione (GSH) and L-cysteine (Cys), in the presence of selective inhibitors of reactive oxygen/nitrogen species (ROS/RNS), Erk1/2, or PI3K/Akt after CEES exposure. Importantly, these metabolite changes were accompanied by a decrease in the glycolytic flux, consistent with the observed decrease in 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) concentration and these CEES-induced phenomena were attenuated by pretreatment of Erk1/2 or PI3-K/Akt inhibitors. On the other hand, CEES exposure disrupts the protein carbonylation (PC) and lipid peroxidation (LPO) in keratinocytes leading to inflammation, crash of the cell-cell communication, cell cycle deregulation, and apoptosis via Erk1/2-PI3K/Akt pathways. However, pretreatment of Erk1/2 or PI3K/Akt inhibitors attenuated the CEES action. Collectively, these results illustrated that accumulated free radicals act as key functional mediators for inflammation, and apoptosis via Erk1/2-PI3K/Akt regulatory signaling cascades induced by CEES exposure. Treatment of pharmacological Erk1/2-PI3K/Akt inhibitors attenuated the CEES-induced keratinocyte injury that may provide the basis for the development of therapeutic strategy to work against CEES exposure.
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PMID:Relevance of Erk1/2-PI3K/Akt signaling pathway in CEES-induced oxidative stress regulates inflammation and apoptosis in keratinocytes. 3080 62