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Query: UNIPROT:P51812 (mitogen-activated protein)
 10,636 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

Bacterial pathogens use type III secretion systems (TTSSs) to deliver virulence factors into eukaryotic cells. These effectors perturb host-defence responses, especially signal transduction pathways. A functional TTSS was identified in the symbiotic, nitrogen-fixing bacterium Rhizobium sp. NGR234. NopL (formerly y4xL) of NGR234 is a putative symbiotic effector that modulates nodulation in legumes. To test whether NopL could interact with plant proteins, in vitro phosphorylation experiments were performed using recombinant nopL protein purified from Escherichia coli as well as protein extracts from Lotus japonicus and tobacco plants. NopL serves as a substrate for plant protein kinases as well as purified protein kinase A. Phosphorylation of NopL was inhibited by the Ser/Thr kinase inhibitor K252a as well as by PD98059, a mitogen-activated protein (MAP) kinase kinase inhibitor. It thus seems likely that, after delivery into the plant cell, NopL modulates MAP kinase pathways.
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PMID:Purification and phosphorylation of the effector protein NopL from Rhizobium sp. NGR234. 1462 78

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

Eicosanoid production is reduced when the nitric oxide (NO.) pathway is inhibited or when the inducible NO synthase gene is deleted, indicating that the NO. and arachidonic acid pathways are linked. We hypothesized that peroxynitrite, formed by the reaction of NO. and superoxide anion, may cause signaling events leading to arachidonic acid release and subsequent eicosanoid generation. Western blot analysis of rat arterial smooth muscle cells demonstrated that peroxynitrite (100-500 microM) and 3-morpholinosydnonimine (SIN-1; 200 microM) stimulate phosphorylation of extracellular signal-regulated kinase (ERK), p38, and cytosolic phospholipase A(2) (cPLA(2)). We found that peroxynitrite-induced arachidonic acid release was completely abrogated by the mitogen-activated protein/ERK kinase (MEK) inhibitor U0126 and by calcium chelators. With the p38 inhibitor SB-20219, we demonstrated that peroxynitrite-induced p38 phosphorylation led to minor arachidonic acid release, whereas U0126 completely blocked p38 phosphorylation. Addition of arachidonic acid caused p38 phosphorylation, suggesting that arachidonic acid or its metabolites are responsible for p38 activation. KN-93, a specific inhibitor of Ca(2+)/calmodulin-dependent kinase II (CaMKII), revealed no role for this kinase in peroxynitrite-induced arachidonic acid release in our cell system. Together, these results show that in response to peroxynitrite the cell initiates the MEK/ERK cascade leading to cPLA(2) activation and arachidonic acid release. Thus studies investigating the role of the NO. pathway on eicosanoid production must consider the contribution of signaling pathways initiated by reactive nitrogen species. These findings may provide evidence for a new role of peroxynitrite as an important reactive nitrogen species in vascular disease.
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PMID:Involvement of the mitogen-activated protein kinase cascade in peroxynitrite-mediated arachidonic acid release in vascular smooth muscle cells. 1474 11

We present an analysis of over 1,100 of the approximately 10,000 predicted proteins encoded by the genome sequence of the filamentous fungus Neurospora crassa. Seven major areas of Neurospora genomics and biology are covered. First, the basic features of the genome, including the automated assembly, gene calls, and global gene analyses are summarized. The second section covers components of the centromere and kinetochore complexes, chromatin assembly and modification, and transcription and translation initiation factors. The third area discusses genome defense mechanisms, including repeat induced point mutation, quelling and meiotic silencing, and DNA repair and recombination. In the fourth section, topics relevant to metabolism and transport include extracellular digestion; membrane transporters; aspects of carbon, sulfur, nitrogen, and lipid metabolism; the mitochondrion and energy metabolism; the proteasome; and protein glycosylation, secretion, and endocytosis. Environmental sensing is the focus of the fifth section with a treatment of two-component systems; GTP-binding proteins; mitogen-activated protein, p21-activated, and germinal center kinases; calcium signaling; protein phosphatases; photobiology; circadian rhythms; and heat shock and stress responses. The sixth area of analysis is growth and development; it encompasses cell wall synthesis, proteins important for hyphal polarity, cytoskeletal components, the cyclin/cyclin-dependent kinase machinery, macroconidiation, meiosis, and the sexual cycle. The seventh section covers topics relevant to animal and plant pathogenesis and human disease. The results demonstrate that a large proportion of Neurospora genes do not have homologues in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. The group of unshared genes includes potential new targets for antifungals as well as loci implicated in human and plant physiology and disease.
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PMID:Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism. 1500 97

We show that the mitogen-activated protein (MAP) kinase pathway that responds to osmotic stress in Aspergillus fumigatus is also involved in nutritional sensing. This MAP kinase regulates conidial germination in response to the nitrogen source and is activated upon starvation for either carbon or nitrogen during vegetative growth.
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PMID:A mitogen-activated protein kinase that senses nitrogen regulates conidial germination and growth in Aspergillus fumigatus. 1507 85

Arginine appears to be a semiessential amino acid in humans during critical illness. Catabolic disease states such as sepsis, injury, and cancer cause an increase in arginine utilization, which exceeds body production, leading to arginine depletion. This is aggravated by the reduced nutrient intake that is associated with critical illness. Arginine depletion may have negative consequences on tissue function under these circumstances. Nutritional regimens containing arginine have been shown to improve nitrogen balance and lymphocyte function, and stimulate arginine transport in the liver. We have studied the effects of stress mediators on arginine transport in vascular endothelium, liver, and gut epithelium. In vascular endothelium, endotoxin stimulates arginine uptake, an effect that is mediated by the cytokine tumor necrosis factor-alpha (TNF-alpha) and by the cyclo-oxygenase pathway. This TNF-alpha stimulation involves the activation of intracellular protein kinase C (PKC). A significant increase in hepatic arginine transport activity also occurs following burn injury and in rats with progressive malignant disease. Surgical removal of the growing tumor results in a normalization of the accelerated hepatic arginine transport within days. Chronic metabolic acidosis and sepsis individually augment intestinal arginine transport in rats and Caco-2 cell culture. PKC and mitogen-activated protein kinases are involved in mediating the sepsis/acidosis stimulation of arginine transport. Understanding the regulation of plasma membrane arginine transport will enhance our knowledge of nutrition and metabolism in seriously ill patients and may lead to the design of improved nutritional support formulas.
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PMID:Arginine transport in catabolic disease states. 1546 94

Nitrogen starvation is one of the signals that induce Candida albicans, the major fungal pathogen of humans, to switch from yeast to filamentous growth. In response to nitrogen starvation, C. albicans expresses the MEP1 and MEP2 genes, which encode two ammonium permeases that enable growth when limiting concentrations of ammonium are the only available nitrogen source. In addition to its role as an ammonium transporter, Mep2p, but not Mep1p, also has a central function in the induction of filamentous growth on a solid surface under limiting nitrogen conditions. When ammonium is absent or present at low concentrations, Mep2p activates both the Cph1p-dependent mitogen-activated protein (MAP) kinase pathway and the cAMP-dependent signalling pathway in a Ras1p-dependent fashion via its C-terminal cytoplasmic tail, which is essential for signalling but dispensable for ammonium transport. In contrast, under ammonium-replete conditions that require transporter-mediated uptake Mep2p is engaged in ammonium transport and signalling is blocked such that C. albicans continues to grow in the budding yeast form. Mep2p is a less efficient ammonium transporter than Mep1p and is expressed at much higher levels, a distinguishing feature that is important for its signalling function. At sufficiently high concentrations, ammonium represses filamentous growth even when the signalling pathways are artificially activated. Therefore, C. albicans has established a regulatory circuit in which a preferred nitrogen source, ammonium, also serves as an inhibitor of morphogenesis that is taken up into the cell by the same transporter that mediates the induction of filamentous growth in response to nitrogen starvation.
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PMID:The Mep2p ammonium permease controls nitrogen starvation-induced filamentous growth in Candida albicans. 1581 22

Reactive oxygen and nitrogen species inhibit or promote cell proliferation by modulating the cell signaling pathways that dictate decisions between cell survival, proliferation, and death. In the growth factor-dependent pathways that regulate mitogenesis, numerous positive and negative effectors of signaling are influenced by physiological fluctuations of oxidants, including receptor tyrosine kinases, small GTPases, mitogen-activated protein kinases, protein phosphatases, and transcription factors. The same mitogenic pathways that are sensitive to oxidant levels also directly regulate the expression of cyclin D1, a labile factor required for progression through the G1 phase on the cell cycle. Because the transition from G0 to G1 is the only phase of the cell cycle that is not regulated by cyclin-dependent kinases, but rather by redox-dependent signaling pathways, expression of cyclin D1 represents a primary regulatory node for the dose-dependent effects of oxidants on the induction of cell growth. We suggest that expression of cyclin D1 represents a useful marker for assessing the integration of proliferative and growth inhibitory effects of oxidants on the redox-dependent signaling events that control reentry into the cell cycle.
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PMID:Redox regulation of cell-cycle re-entry: cyclin D1 as a primary target for the mitogenic effects of reactive oxygen and nitrogen species. 1589 20

Reactive oxygen or nitrogen species (RONS) are produced during exercise due, at least in part, to the activation of xanthine oxidase. When exercise is exhaustive they cause tissue damage; however, they may also act as signals inducing specific cellular adaptations to exercise. We have tested this hypothesis by studying the effects of allopurinol-induced inhibition of RONS production on cell signalling pathways in rats submitted to exhaustive exercise. Exercise caused an activation of mitogen-activated protein kinases (MAPKs: p38, ERK 1 and ERK 2), which in turn activated nuclear factor kappaB (NF-kappaB) in rat gastrocnemius muscle. This up-regulated the expression of important enzymes associated with cell defence (superoxide dismutase) and adaptation to exercise (eNOS and iNOS). All these changes were abolished when RONS production was prevented by allopurinol. Thus we report, for the first time, evidence that decreasing RONS formation prevents activation of important signalling pathways, predominantly the MAPK-NF-kappaB pathway; consequently the practice of taking antioxidants before exercise may have to be re-evaluated.
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PMID:Decreasing xanthine oxidase-mediated oxidative stress prevents useful cellular adaptations to exercise in rats. 1593 96


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