Disease relevance of Extracellular Space

• Heme proteins such as myoglobin or hemoglobin, when released into the extracellular space, can instigate tissue toxicity [1].
• Adenosine deaminase, an enzyme that deaminates adenosine to inosine and is limited to the extracellular space, significantly attenuated (61%) the atria-to-His-bundle interval prolongation caused by hypoxia [2].
• The appearance of superoxide anion radical in cerebral extracellular space during and after acute hypertension induced by intravenous norepinephrine was investigated in anesthetized cats equipped with cranial windows [3].
• The finding that human neutrophils contain an intracellular pool of VEGF, secreted in the extracellular space under PMA-, fMet-Leu-Phe-, and TNF-alpha-induced degranulation, suggests a role for human neutrophils as cellular effectors of physiologic as well as pathologic angiogenesis [4].
• Its secretion into the extracellular space indicates furthermore, that it may be an important component of the "proteinase cascade" associated with tumor invasion and metastasis [5].

Psychiatry related information on Extracellular Space

• Aggregation of the amyloid-beta (Abeta) peptide in the extracellular space of the brain is central to Alzheimer's disease pathogenesis [6].
• The disturbances in tryptophan metabolism in unipolar affective disorder had led to reduced amounts of this amino acid in the extracellular space [7].
• Thus, a functionally significant amount of 5HT is present in the extracellular space within the XII nucleus region, and its decrement during carbachol-induced, REM sleep-like atonia is likely to reflect that occurring during natural REM sleep; this may contribute to the decreased tone of upper airway muscles and airway patency [8].

High impact information on Extracellular Space

• Mechanistically, we found that Emilin1 inhibits TGF-beta signaling by binding specifically to the proTGF-beta precursor and preventing its maturation by furin convertases in the extracellular space [9].
• In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human [10].
• The low density lipoprotein receptor-related protein (LRP) is a large multifunctional clearance receptor that has been implicated in the hepatic uptake of chylomicron remnants and in the removal of protease-inhibitor complexes from the circulation and from the extracellular space [11].
• These results provide the first evidence that prion proteins assemble into filaments within the brain and that these filaments accumulate in extracellular spaces to form amyloid plaques [12].
• As a consequence, glutamate levels increase in the extracellular space of Per2(Brdm1) mutant mouse brains [13].

Chemical compound and disease context of Extracellular Space

• The distribution of the lesions in the hypothalamus was similar to that produced by goldthioglucose, and consisted ultrastructurally of marked distention and edema of the extracellular space, with no confined to the dorsal aspect, in the region of the area postrema [14].
• At a concentration that was not toxic by itself, L-trans-pyrrolidine-2,4-dicarboxylate increased the toxicity of glutamate approximately fivefold and slowed the clearance of glutamate from the extracellular space [15].
• We conclude that a dysfunction of the BBB, of a degree known to induce brain edema (10 mg of protamine sulfate), significantly increases the extracellular concentration of excitatory amino acids, GABA, taurine, and phosphoethanolamine in the extracellular space [16].
• We investigated the pharmacokinetics of piperacillin and tazobactam in the extracellular space fluid of inflamed soft tissues of six patients with diabetic foot infection using in vivo microdialysis and found similar penetration for piperacillin but not for tazobactam into inflamed and noninflamed soft tissue [17].
• 4. Also at 21-22 degrees neither stimulation nor anoxia generated more than minimal reductions in extracellular space [by 2.3 +/- 0.94%, as measured by the tetramethylammonium (TMA) method], and spreading depression (SD) occurred in only 1 out of 20 slices [18].

Biological context of Extracellular Space

• Analysis of excitatory synaptic transmission in the rat hypothalamic supraoptic nucleus revealed that glutamate clearance and, as a consequence, glutamate concentration and diffusion in the extracellular space, is associated with the degree of astrocytic coverage of its neurons [19].
• As the concentration of zinc in the extracellular spaces of the brain is higher than that for copper, we put forward the hypothesis that PrP is involved in neuronal zinc homeostasis; PrP might be involved in transport of zinc into the cell or might act as a zinc sensor [20].
• Jejunal biopsy revealed a significant increase in dilatation of intercellular spaces in patients compared to controls; this increase was not correlated with hepatic wedge pressure, but was significantly inversely correlated to plasma renin and aldosterone concentration [21].
• After endocytosis, transferrin was released, apparently intact, into the extracellular space [22].
• The results suggest that certain cutin-related fatty acids synthesized by CYP86A2 may repress bacterial type III gene expression in the intercellular spaces [23].

Anatomical context of Extracellular Space

• These highly tissue-specific abnormalities are associated with profound defects in the elastic fiber structure and with a reduced deposition of TGF-beta in the extracellular space [24].
• Electron micrographs revealed dilatation of lateral intercellular spaces and disruption of desmosomes in tissues exposed to urea, but no visible alterations in tissues exposed to solutions containing sucrose [25].
• The glucose concentration in the extracellular space of subcutaneous adipose tissue closely mirrors the blood glucose concentration [26].
• The extracellular space in intact, isolated gap junctions is too small to permit binding of antibody molecules, necessitating the experimental separation of the junctional membranes to expose their extracellular surfaces using a urea/alkali procedure [27].
• When chondrocytes spread on the culture dish, CSPG is deposited in the extracellular space as an amorphous mass and fibronectin forms fine, intercellular strands, whereas type II collagen disappears from the chondrocyte surface and remains absent from the extracellular space in early cultures [28].

Associations of Extracellular Space with chemical compounds

• When the extracellular [K+] rises in brain ischaemia, uptake reverses, releasing glutamate into the extracellular space [29].
• Tonic activation of adenosine receptors by adenosine that is normally present in the extracellular space in brain tissue leads to inhibitory effects that appear to be mediated by both adenosine A1 and A2A receptors [30].
• For amino acids and monoamines, this is achieved by their uptake into the cell by specific high-affinity transporters; acetylcholine is first broken down in the extracellular space and then choline is taken up by the cell [31].
• Images of the intrinsic optical signal acquired during these slice experiments indicated that furosemide coincidentally blocked changes in extracellular space [32].
• The cell-cell channels are permeable to relatively large molecules, and it was thought that opening of hemichannels to the extracellular space would kill cells through loss of metabolites, collapse of ionic gradients and influx of Ca(2+) [33].

Gene context of Extracellular Space

• We used genetic and immunological assays to show that CLV3 localizes to the apoplast and that export to the extracellular space is required for its function in activating the CLV1/CLV2 receptor complex [34].
• It is widely believed that these Abeta peptides are secreted into the extracellular spaces of the CNS, where they assemble into toxic oligomers that kill neurons and eventually form deposits of senile plaques [35].
• Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder [36].
• Thus, TGase 2-catalyzed protein polymerization contributes to the ultrastructural changes typical of dying apoptotic cells; it stabilizes the integrity of the apoptotic cells, preventing the release of harmful intracellular components into the extracellular space and, consequently, inflammation and scar formation [37].
• The presence of a motif in BRCA1 characteristic of a family of proteins known as granins, has led to the suggestion that the protein is secreted into the extracellular space [38].

Analytical, diagnostic and therapeutic context of Extracellular Space

• By immunofluorescence double staining of the newly formed cartilage matrix, we demonstrate that CSPG spreads farther out into the extracellular space that type II collagen [28].
• Apo D protein (Mr 32.8 kd) was secreted and accumulated in the endoneurial extracellular space where it could be detected in lipoprotein fractions by immunoblotting using established antibodies to human Apo D [39].
• Information about the structure of the paired helical filaments (PHF) that accumulate within human neurons and the amyloid fibers that accumulate in the extracellular spaces between neurons in Alzheimer disease has so far depended on electron microscopy of thin-sectioned or negatively stained material [40].
• Indirect immunofluorescence studies showed that lysyl oxidase was present in association with collagen in the extracellular space [41].
• Following the intravenous injection of angiotensin II antibodies (purified by affinity chromatography), the plasma concentration of the antibodies declined in a two-exponential curve with half times of 11 hours and 7 days, which probably reflect distribution in the extracellular space and elimination, respectively [42].

References