Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine receptors modulate neuronal and synaptic function in a range of ways that may make them relevant to the occurrence, development and treatment of brain ischemic damage and degenerative disorders. A(1) adenosine receptors tend to suppress neural activity by a predominantly presynaptic action, while A(2A) adenosine receptors are more likely to promote transmitter release and postsynaptic depolarization. A variety of interactions have also been described in which adenosine A(1) or A(2) adenosine receptors can modify cellular responses to conventional neurotransmitters or receptor agonists such as glutamate, NMDA, nitric oxide and P2 purine receptors. Part of the role of adenosine receptors seems to be in the regulation of inflammatory processes that often occur in the aftermath of a major insult or disease process. All of the adenosine receptors can modulate the release of cytokines such as interleukins and tumor necrosis factor-alpha from immune-competent leukocytes and glia. When examined directly as modifiers of brain damage, A(1) adenosine receptor (AR) agonists, A(2A)AR agonists and antagonists, as well as A(3)AR antagonists, can protect against a range of insults, both in vitro and in vivo. Intriguingly, acute and chronic treatments with these ligands can often produce diametrically opposite effects on damage outcome, probably resulting from adaptational changes in receptor number or properties. In some cases molecular approaches have identified the involvement of ERK and GSK-3beta pathways in the protection from damage. Much evidence argues for a role of adenosine receptors in neurological disease. Receptor densities are altered in patients with Alzheimer's disease, while many studies have demonstrated effects of adenosine and its antagonists on synaptic plasticity in vitro, or on learning adequacy in vivo. The combined effects of adenosine on neuronal viability and inflammatory processes have also led to considerations of their roles in Lesch-Nyhan syndrome, Creutzfeldt-Jakob disease, Huntington's disease and multiple sclerosis, as well as the brain damage associated with stroke. In addition to the potential pathological relevance of adenosine receptors, there are earnest attempts in progress to generate ligands that will target adenosine receptors as therapeutic agents to treat some of these disorders.
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PMID:Adenosine receptors and neurological disease: neuroprotection and neurodegeneration. 1963 93

Due to the frequency of occurrence of cardiovascular disease and its course full of severe complications, patients with this condition make a special population. This group is the addressee of the preventive actions included in secondary prevention. The goal of these actions is a reduction of frequency of the occurrence of consecutive incidents connected with ischemic heart disease, ischemic stroke and peripheral artery disease. The actions put a special emphasis on the counteraction of significant and negative from the social-economic point of view phenomenon, such as disability and premature deaths. The key role within the frames of the integrated preventive procedure in the patients with cardiovascular disease plays the modification of physical activity, mainly realized as a part of a supervised physical training. The training is a basic element of a systematized cardiac rehabilitation. It was Hellerstain, who as a pioneer in using this kind of rehabilitation in the patients after acute coronary incidents, and in the 1950s began propagating a multi-disciplinary attitude to the cardiac rehabilitation programs. Since WHO's formulation of the first definition of cardiac rehabilitation in 1964, as a result of the achievements of modern invasive cardiology, cardiosurgery and pharmacotherapy, the procedures of treatment of the patients with acute coronary syndrome changed radically. Moreover, a time of their hospitalization has shortened significantly. This fact had an influence on created by many scientific associations the successive development of the standardized process of convalescence, which is cardiac rehabilitation. The Board of Polish Society of Cardiology (PTK), appreciating the rank of the issue, appointed a group of experts to work on the standards of the cardiac rehabilitation, which were published in 2004 in the journal "Folia Cardiologica". Based on the modified in 2003 requirements established by The Working Group of Rehabilitation and Effort Physiology of European Society of Cardiology and the authors' own experiences, they standardize the regulations of the cardiac rehabilitation. What is specially underlined in this document is keeping the regulation of cardiac rehabilitation effects optimization with maximum safety for the patients and recommending wide, not depending on age, access to complex rehabilitation programs, which contains multi-factor interventive actions. Promoting all aspects of the improvement of physical activity, the cardiac rehabilitation programs contribute to the large extent to the positive modification of arthrosclerosis risk factors, the improvement of physical performance and reducing the risk of occurrence of next acute cardiovascular incidences. All the above-mentioned aspects lead to a comeback to active participation in the social life, and consequently have a positive influence on the quality of life of the people with cardiovascular disease. The aim of this work is summing up the present knowledge of cardiac rehabilitation as a basic element of secondary prevention.
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PMID:[Complex cardiac rehabilitation in a strategy of secondary prevention of cardiovascular disease]. 1965 Apr 26

The Neurovascular Education and Training in Stroke Management and Acute Reperfusion Therapy (NET SMART) program for advanced practice nursing (APN) offers a first-of-its-kind, academic, postgraduate, fellowship program for APNs that is modeled after physician academic fellowship programs but supported by a flexible Internet-based platform. This article details the rationale, methods, and preliminary results of the NET SMART APN experience, which serves as a unique template for the development of academic postgraduate nursing fellowship programs across a variety of specialty practices.
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PMID:Postgraduate fellowship education and training for nurses: the NET SMART experience. 1995 62

Activated protein C (APC) is a vitamin-K dependent natural anticoagulant protein. With its function in blood clotting reaction, APC can reduce the risk of venous thrombosis to prevent ischemic disease. A number of in vivo and in vitro studies over the past few decades have revealed that APC also exerted cytoprotective effects to decrease the mortality caused by endotoxin, sepsis, and brain ischemic stroke. The direct cytoprotective role requires APC binding to the endothelial protein C receptor (EPCR) and activating protease activated receptor-1 (PAR-1). It is now believed that the beneficial characters of APC are partially independent from its anticoagulant activity, though more studies need to be done to demonstrate the exact molecular mechanism. In this review, we have linked the cytoprotective effects of APC including the anti-inflammatory and anti-apoptosis activities to myocardial ischemic injury caused by cardiac ischemia reperfusion. Specifically, we have tried to combine the potential signaling pathways initiated by APC with the well-known adaptive signaling such as AMP-activated protein kinase (AMPK), PI3K/Akt and ERK/MAPK pathways that contribute to the cardioprotection against myocardial ischemia injury. We speculate that APC protects against cardiac ischemia injury via triggering crucial cardioprotective signaling pathways, and these effects are mostly associated with its cytoprotective activity but independent on its anticoagulant activity.
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PMID:Activated protein C: a potential cardioprotective factor against ischemic injury during ischemia/reperfusion. 1995 50

The use of opioid analgesics has a long history in clinical settings, although the functions of opioid receptors, especially their role in the brain, are not well understood yet. Recent studies have generated abundant new data on opioid receptor-mediated functions and the underlying mechanisms. The most exciting finding in the past decade is probably the neuroprotection against hypoxic/ischemic stress mediated by delta-opioid receptors (DOR). An up-regulation of DOR expression and the release of endogenous opioids may increase neuronal tolerance to hypoxic/ischemic stress. The DOR signal triggers, depending on stress duration and severity, different mechanisms at multiple levels to preserve neuronal survival, including the stabilization of ionic homeostasis, an increase in pro-survival signaling (e.g., PKC-ERK-Bcl 2) and the enhanced anti-oxidative capacity. Recent data on DOR-mediated neuroprotection provide us a new concept of neuroprotection against neurological disorders and have a potentially significant impact on the prevention and treatment of some serious neurological conditions, such as stroke.
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PMID:A novel insight into neuroprotection against hypoxic/ischemic stress. 2002 93

Atrial fibrillation (AF) is a common arrhythmia that increases the risk of stroke and heart failure. Here, we have shown that mast cells, key mediators of allergic and immune responses, are critically involved in AF pathogenesis in stressed mouse hearts. Pressure overload induced mast cell infiltration and fibrosis in the atrium and enhanced AF susceptibility following atrial burst stimulation. Both atrial fibrosis and AF inducibility were attenuated by stabilization of mast cells with cromolyn and by BM reconstitution from mast cell-deficient WBB6F1-KitW/W-v mice. When cocultured with cardiac myocytes or fibroblasts, BM-derived mouse mast cells increased platelet-derived growth factor A (PDGF-A) synthesis and promoted cell proliferation and collagen expression in cardiac fibroblasts. These changes were abolished by treatment with a neutralizing antibody specific for PDGF alpha-receptor (PDGFR-alpha). Consistent with these data, upregulation of atrial Pdgfa expression in pressure-overloaded hearts was suppressed by BM reconstitution from WBB6F1-KitW/W-v mice. Furthermore, injection of the neutralizing PDGFR-alpha-specific antibody attenuated atrial fibrosis and AF inducibility in pressure-overloaded hearts, whereas administration of homodimer of PDGF-A (PDGF-AA) promoted atrial fibrosis and enhanced AF susceptibility in normal hearts. Our results suggest a crucial role for mast cells in AF and highlight a potential application of controlling the mast cell/PDGF-A axis to achieve upstream prevention of AF in stressed hearts.
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PMID:Cardiac mast cells cause atrial fibrillation through PDGF-A-mediated fibrosis in pressure-overloaded mouse hearts. 2003 2

Exercise preconditioning induces neuroprotection after stroke. We investigated the beneficial role of heat shock protein-70 (HSP-70) and phosphorylated extracellular-signal-regulated-kinase 1/2 (pERK 1/2), as they pertain to reducing apoptosis and their influence on Bcl-x(L), Bax, and apoptosis-inducing factor (AIF) in rats subjected to ischemia and reperfusion. Adult male Sprague-Dawley rats were subjected to 30 min of exercise on a treadmill for 1, 2, or 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Protein levels of HSP-70, pERK 1/2, Bcl-x(L), Bax, and AIF were analyzed using Western blot. Neuroprotection was based on levels of apoptosis (TUNEL) and infarct volume (Nissl staining). Immunocytochemistry was used for cellular expression of HSP-70 and pERK 1/2. Significant (P<0.05) up-regulation of HSP-70 and pERK 1/2 after 3 weeks of exercise coincided with significant (P<0.05) reduction in neuronal apoptosis and brain infarct volume. Inhibition of either one of these two factors showed a significant (P<0.05) reversal in the neuroprotection. Bax and AIF were down-regulated, while levels of Bcl-x(L) were up-regulated in response to stroke after exercise. Inhibiting HSP-70 or pERK 1/2 reversed this resultant increase or decrease. Our results indicate that exercise diminishes neuronal injury in stroke by up-regulating HSP-70 and ERK 1/2.
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PMID:Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2. 2008 67

Neurogenesis occurs in the cerebral cortex of adult rats after focal cerebral ischemia. Whether or not the newborn neurons could synthesize neurotransmitters is unknown. To elucidate such a possibility, a photothrombotic ring stroke model with spontaneous reperfusion was induced in adult male Wistar rats. The DNA duplication marker BrdU was repeatedly injected, and the rats were sacrificed at various times after stroke. To detect BrdU nuclear incorporation and various neurotransmitters, brain sections were processed for single/double immunocytochemistry and single/double/triple immunofluorescence. Stereological cell counting was performed to assess the final cell populations. At 48 h, 5 days, 7 days, 30 days, 60 days and 90 days after stroke, numerous cells were BrdU-immunolabeled in the penumbral cortex. Some of these were doubly immunopositive to the cholinergic neuron-specific marker ChAT or GABAergic neuron-specific marker GAD. As analyzed by 3-D confocal microscopy, the neurotransmitters acetylcholine and GABA were colocalized with BrdU in the same cortical cells. In addition, GABA was colocalized with the neuron-specific marker Neu N in the BrdU triple-immunolabeled cortical cells. This study suggests that the newborn neurons are capable of synthesizing the neurotransmitters acetylcholine and GABA in the penumbral cortex, which is one of the fundamental requisites for these neurons to function in the poststroke recovery.
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PMID:Neurotransmitter synthesis in poststroke cortical neurogenesis in adult rats. 2008 68

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease and conditions such as ischemic stroke affect millions of individuals annually and exert an enormous financial burden on society. A hallmark of these conditions is the abnormal loss of neurons. Currently, there are no effective strategies to prevent neuronal death in these pathologies. We report that several 2-arylidine and 2-hetarylidin derivatives of the 1,4-benzoxazines class of compounds are highly protective in tissue culture models of neurodegeneration. Results obtained using pharmcalogical inhibitors indicate that neuroprotection by these compounds does not involve the Raf-MEK-ERK or PI-3 kinase-Akt signaling pathways nor other survival-promoting molecules such as protein kinase A (PKA), calcium calmodulin kinase A (CaMK), and histone deacetylases (HDACs). We tested one of these compounds, (Z)-6-amino-2-(3',5'-dibromo-4'-hydroxybenzylidene)-2H-benzo[b][1,4]oxazin-3(4H)-one, designated as HSB-13, in the 3-nitropropionic acid (3-NP)-induced mouse model of Huntington's disease. HSB-13 reduced striatal degeneration and improved behavioral performance in mice administered with 3-NP. Furthermore, HSB-13 was protective in a Drosophila model of amyloid precursor protein (APP) toxicity. To understand how HSB-13 and other 1,4-benzoxazines protect neurons, we performed kinase profiling analyses. These analyses showed that HSB-13 inhibits GSK3, p38 MAPK, and cyclin-dependent kinases (CDKs). In comparison, another compound, called ASK-2a, that protects cerebellar granule neurons against low-potassium-induced death inhibits GSK3 and p38 MAPK but not CDKs. Despite its structural similarity to HSB-13, however, ASK-2a is incapable of protecting cortical neurons and HT22 cells against homocysteic acid (HCA)-induced or Abeta toxicity, suggesting that protection against HCA and Abeta depends on CDK inhibition. Compounds described in this study represent a novel therapeutic tool in the treatment of neurodegenerative diseases.
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PMID:Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration. 2014 21

Reactive astrocytes are traditionally thought to impede brain plasticity after stroke. However, we previously showed that reactive astrocytes may also contribute to stroke recovery, partly via the release of a nuclear protein called high-mobility group box 1 (HMGB1). Here, we investigate the mechanisms that allow stimulated astrocytes to release HMGB1. Exposure of rat primary astrocytes to IL-1beta for 24 h elicited a dose-dependent HMGB1 response. Immunostaining and western blots of cell lysates showed increased intracellular levels of HMGB1. Western blots confirmed that IL-1beta induced a release of HMGB1 into astrocyte conditioned media. MAP kinase signaling was involved. Levels of phospho-ERK were increased by IL-1beta, and the MEK/ERK inhibitor U0126 decreased HMGB1 upregulation in the stimulated astrocytes. Since HMGB1 is a nuclear protein, the role of the nuclear protein exporter, chromosome region maintenance 1 (CRM1), was assessed as a candidate mechanism for linking MAP kinase signaling to HMGB1 release. IL-1beta increased CRM1 expression in concert with a translocation of HMGB1 from nucleus into cytoplasm. Blockade of IL-1beta-stimulated HMGB1 release with the ERK inhibitor U0126 was accompanied by a downregulation of CRM1. Our findings reveal that IL-1beta stimulates the release of HMGB1 from activated astrocytes via ERK MAP kinase and CRM1 signaling. These data suggest a novel pathway by which inflammatory cytokines may enhance the ability of reactive astrocytes to release prorecovery mediators after stroke.
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PMID:Role of ERK map kinase and CRM1 in IL-1beta-stimulated release of HMGB1 from cortical astrocytes. 2022 44


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