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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventional kinesin is a motor protein that moves stepwise along microtubules carrying membrane-bound organelles toward the periphery of cells. The steps are of amplitude 8.1 nm, the distance between adjacent tubulin binding sites, and are powered by the hydrolysis of ATP. We have asked: how many steps does kinesin take for each molecule of ATP that it hydrolyzes? To answer this question, the motility and ATP hydrolysis of recombinant, heterotetrameric and homodimeric conventional Drosophila kinesins adsorbed to 200-nm-diameter casein-coated silica beads were assayed under identical, single-molecule conditions. Division of the speed by the maximum microtubule-activated ATPase rate gave a stoichiometry of 1. 08 +/- 0.09 steps for each ATP hydrolyzed at 1 mM ATP. Therefore, under low loads in which the drag force << 1 pN, coupling between the chemical and mechanical cycles of kinesin is tight, consistent with conventional power stroke models. Our results rule out models that require two or more ATPs/step, such as some thermal ratchet models, or that propose multiple steps powered by single ATPs.
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PMID:Kinesin takes one 8-nm step for each ATP that it hydrolyzes. 992 Sep 16

Plasma angiotensin I-converting enzyme (ACE) levels are different between the stroke-prone spontaneously hypertensive rat (SHRSPHD) and the normotensive Wistar-Kyoto (WKYHD) rat. This interstrain variability in plasma ACE levels is independent of blood pressure and is genetically linked to the ACE gene. The present study explored the hypothesis of an interstrain variability of tissue ACE activity and ACE gene expression levels. Tissue ACE levels were studied by enzymic activity measurement in the membrane fraction, and ACE mRNA levels were quantified by solution hybridization-ribonuclease protection assay. In lung, heart, kidney, and duodenum, membrane-bound ACE activity and ACE mRNA amount were significantly higher in WKYHD rats compared with SHRSPHD rats. No difference was observed in the testis where a specific isoform of the enzyme is produced. Our results suggest that in addition to determine differential plasma ACE levels between the WKYHD and SHRSPHD strains, the interstrain genetic variability also determines differential ACE mRNA and membrane-bound enzyme levels in somatic tissues. This likely reflects a difference in the ACE gene expression due to genetically determined regulatory mechanisms operative in all somatic tissues.
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PMID:Interstrain differences in angiotensin I-converting enzyme mRNA and activity levels. Comparison between stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats. 1036 81

Atherosclerosis constitutes the most common medical and surgical problem. This can be manifested clinically as stroke, coronary artery disease, or peripheral vascular disease. In the present review the microscopic appearance of the normal arterial wall, the definition of atherosclerosis and the five theories of atherogenesis are described. These are: the lipid theory, the hemodynamic theory, the fibrin incrustation theory, the nonspecific mesenchymal hypothesis and the response to injury hypothesis. Based on the above theories the sequence of events in atherogenesis is analyzed. The classification of the atherosclerotic lesions according to Stary (types I-VI) and their characteristics appear in a table. The epidemiology and the role of the following risk factors are presented in detail: age, sex, lipid abnormalities, cigarette smoking, hypertension, diabetes mellitus, physical inactivity, alcohol consumption, obesity, and hemostatic factors. In addition, less common genetically determined associations like homocystinuria, Tangier disease, Hutchinson-Gilford syndrome (progeria), Werner's syndrome, radiation induced atherosclerosis and the implications of Chlamydia pneumoniae on the arterial wall are discussed.
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PMID:The genesis of atherosclerosis and risk factors: a review. 1122 92

Antiphospholipid antibodies are associated with venous and arterial thrombo-occlusive events, including stroke. They are a heterogeneous family of antibodies that react to negatively charged membrane-bound phospholipids or phospholipid-protein complexes. Despite much progress in the past decade, the precise mechanisms by which they promote thrombosis remain unknown. Increased risk of initial, but perhaps not recurrent, stroke has been associated with their presence. Antithrombotic regimens have been the mainstay of treatment, but the ideal therapeutic approach remains to be defined. This paper reviews the history, definition, associations, and treatment of this complex entity.
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PMID:Antiphospholipid antibodies and stroke. 1475 58

The central nervous system has the second highest concentration of lipids after adipose tissue. Long chain fatty acids, particularly arachidonic acid and docosahexaenoic acid, are integral components of neural membrane phospholipids. Alterations in neural membrane phospholipid components cannot only influence crucial intracellular and intercellular signaling but also alter many membrane physical properties such as fluidity, phase transition temperature, bilayer thickness, and lateral domains. A deficiency of docosahexaenoic acid markedly affects neurotransmission, membrane-bound enzyme and ion channel activities, gene expression, intensity of inflammation, and immunity and synaptic plasticity. Docosahexaenoic acid deficiency is associated with normal aging, Alzheimer disease, hyperactivity, schizophrenia, and peroxisomal disorders. Although the molecular mechanism of docosahexaenoic acid involvement in the disorders remains unknown, the supplementation of docosahexaenoic acid in the diet restores gene expression and modulates neurotransmission. Also, improvements are seen in signal transduction processes associated with behavioral deficits, learning activity, peroxisomal disorders, and psychotic changes in schizophrenia, depression, hyperactivity, stroke, and Alzheimer disease.
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PMID:Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function. 1504 Oct 28

The precise role of microglia in stroke and cerebral ischemia has been the subject of debate for a number of years. Microglia are capable of synthesizing numerous soluble and membrane-bound biomolecules, some known to be neuroprotective, some neurotoxic, whereas others have less definitive bioactivities. The molecular mechanisms through which microglia activate these molecules have thus become an important area of ischemia research. Here we provide a survey review that summarizes the key actions of microglial factors in cerebral ischemia including complement proteins, chemokines, pro-inflammatory cytokines, neurotrophic factors, hormones, and proteinases, as well several important messenger molecules that play a part in how these factors respond to extracellular signals during ischemic injuries. We also provide some new perspectives on how microglial intracellular signaling may contribute to the seemingly contradictory roles of several microglial effector molecules.
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PMID:Microglia in cerebral ischemia: molecular actions and interactions. 1684 90

Novel and diverse functions of glial cells are currently the focus of much attention [A. Volterra and J. Meldolesi (2005) Nature Rev. 6, 626-640]. Here we present evidence that rat astroglia release acetylcholinesterase (AChE) as part of their response to hypoxic damage. Exposure of astroglia to tert-butyl hydroperoxide, and hence oxidative stress, subsequently leads to a switching in mRNA from the classical membrane-bound T-AChE to a preferential increase in the splice variant for a soluble form, R-AChE, This change in expression is reflected in increased perinuclear and reduced cytoplasmic AChE staining of the insulted glial cells, with a concomitant and marked increase in extracellular secretion that peaks at 1 h post-treatment. An analogous increase in R-AChE, over a similar time scale, occurs in response to psychological stress [D. Kaufer et al. (1998) Nature 93, 373-377], as well as to head injury and stroke [E. Shohami et al. (1999) J. Neurotrauma 6, 365-76]. The data presented here suggest that glial cells may be key chemical intermediaries in such situations and, perhaps more generally in pathological conditions involving oxidative stress, such as neurodegeneration.
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PMID:Astroglia up-regulate transcription and secretion of 'readthrough' acetylcholinesterase following oxidative stress. 1690 48

The membrane-anchored metalloproteinase tumor necrosis factor-alpha-converting enzyme (TACE/a disintegrin and metalloproteinase [ADAM] 17) is key in proteolytic ectodomain shedding of several membrane-bound growth factors, cytokines and receptors. The expression and activity of ADAM17 increases under some pathological conditions including stroke, and promotes neural progenitor cell migration and contributes to stroke-induced neurogenesis. Hypoxia initiates cellular invasive processes that occur under both physiological and pathological conditions such as invasion and metastasis of some tumors. In the present study, we sought to elucidate whether ADAM17 contributes to brain tumor invasion. To this end, we examined the role of ADAM17 in the invasiveness of two different brain tumor cell lines, 9L rat gliosarcoma and U87 human glioma, under normoxic and hypoxic conditions. Additionally, we tested the effects of ADAM17 suppression on in vitro tumor cell invasion by means of ADAM17 proteolytic inhibitors and specific small interfering RNA. We found that tumor cells upregulated ADAM17 expression under hypoxia, and that ADAM17 activity correlated with increased tumor cell invasion. Conversely, suppression of ADAM17 proteolysis decreased invasiveness induced by hypoxia in 9L and U87 cells. Furthermore, the contribution of ADAM17 to tumor invasion was independent of matrix metalloproteinase (MMP)-2 and MMP-9 activity. ADAM17 was also found to activate the epidermal growth factor/phosphoinositide-3 kinase/serine/threonine kinase signal transduction pathway. Our data suggest that hypoxia-induced ADAM17 contributes to glioma cell invasiveness through activation of the EGFR signal pathway.
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PMID:Inhibition of ADAM17 reduces hypoxia-induced brain tumor cell invasiveness. 1735 61

The Notch pathway is a highly conserved and ubiquitous signaling system that functions in determining a diverse array of cell fates and regulates many cellular processes during embryonic development and throughout adulthood. Links to cancer, stroke and Alzheimer's disease underscore the need to define the molecular basis of Notch activation. Notch signaling is induced through direct cell-cell interactions that promote receptor activation following engagement with a membrane-bound Delta, Serrate, Lag-2 (DSL) ligand on adjacent cells. Cells take on distinct fates because Notch signaling is consistently activated in only one of the two interacting cells, highlighting the importance of establishing and maintaining signaling polarity. Studies in flies and worms have identified positive and negative transcriptional feedback mechanisms that amplify small differences in Notch and DSL ligand expression to bias which cells send or receive signals. However, endocytosis by signal-sending and signal-receiving cells also appears critical for directing and regulating Notch activation. In particular, endocytosis and membrane trafficking of DSL ligands, Notch and modulators can determine the competence of cells to send or receive signals that ensure reproducibility in generating cell types regulated by Notch signaling.
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PMID:Notch signaling--constantly on the move. 1754

Prostaglandin E(2) (PGE(2)) is the most abundant prostaglandin in the human body. It has a large number of biological actions that it exerts via four types of receptors, EP1-4. PGE(2) is formed from arachidonic acid by cyclooxygenase (COX-1 and COX-2)-catalyzed formation of prostaglandin H(2) (PGH(2)) and further transformation by PGE synthases. The isomerization of the endoperoxide PGH(2) to PGE(2) is catalyzed by three different PGE synthases, viz. cytosolic PGE synthase (cPGES) and two membrane-bound PGE synthases, mPGES-1 and mPGES-2. Of these isomerases, cPGES and mPGES-2 are constitutive enzymes, whereas mPGES-1 is mainly an induced isomerase. cPGES uses PGH(2) produced by COX-1 whereas mPGES-1 uses COX-2-derived endoperoxide. mPGES-2 can use both sources of PGH(2). mPGES-1 is a member of the membrane associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) superfamily. It requires glutathione as an essential cofactor for its activity. mPGES-1 is up-regulated in response to various proinflammatory stimuli with a concomitant increased expression of COX-2. The coordinate increased expression of COX-2 and mPGES-1 is reversed by glucocorticoids. Differences in the kinetics of the expression of the two enzymes suggest distinct regulatory mechanisms for their expression. Studies, mainly from disruption of the mPGES-1 gene in mice, indicate key roles of mPGES-1-generated PGE(2) in female reproduction and in pathological conditions such as inflammation, pain, fever, anorexia, atherosclerosis, stroke, and tumorigenesis. These findings indicate that mPGES-1 is a potential target for the development of therapeutic agents for treatment of several diseases.
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PMID:Membrane prostaglandin E synthase-1: a novel therapeutic target. 1787 11


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