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Extracellular Compartments (extracellular + compartment)
Selected AbstractsEffects of immersion water temperature on whole-body fluid distribution in humansACTA PHYSIOLOGICA, Issue 1 2004J. M. Stocks Abstract Aim:, In this study, we quantified acute changes in the intracellular and extracellular fluid compartments during upright neutral- and cold-water immersion. We hypothesized that, during short-term cold immersion, fluid shifts would be wholly restricted to the extracellular space. Methods:, Seven males were immersed 30 days apart: control (33.3 ° SD 0.6 °C); and cold (18.1 ° SD 0.3 °C). Posture was controlled for 4 h prior to a 60-min seated immersion. Results:, Significant reductions in terminal oesophageal (36.9 ° ± 0.1 °,36.3 ° ± 0.1 °C) and mean skin temperatures (30.3 ° ± 0.3 °,23.0 ° ± 0.3 °C) were observed during the cold, but not the control immersion. Both immersions elicited a reduction in intracellular fluid [20.17 ± 6.02 mL kg,1 (control) vs. 22.72 ± 9.90 mL kg,1], while total body water (TBW) remained stable. However, significant plasma volume (PV) divergence was apparent between the trials at 60 min [12.5 ± 1.0% (control) vs. 6.1 ± 3.1%; P < 0.05], along with a significant haemodilution in the control state (P < 0.05). Plasma atrial natriuretic peptide concentration increased from 18.0 ± 1.6 to 58.7 ± 15.1 ng L,1 (P < 0.05) during cold immersion, consistent with its role in PV regulation. We observed that, regardless of the direction of the PV change, both upright immersions elicited reductions in intracellular fluid. Conclusion:, These observations have two implications. First, one cannot assume that PV changes reflect those of the entire extracellular compartment. Second, since immersion also increases interstitial fluid pressure, fluid leaving the interstitium must have been rapidly replaced by intracellular water. [source] Paradoxical roles for lysyl oxidases in cancer,A prospectJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2007Stacey L. Payne Abstract Lysyl oxidase (LOX) is an extracellular matrix (ECM) enzyme that catalyzes the cross-linking of collagens or elastin in the extracellular compartment, thereby regulating the tensile strength of tissues. However, recent reports have demonstrated novel roles for LOX, including the ability to regulate gene transcription, motility/migration, and cell adhesion. These diverse functions have led researchers to hypothesize that LOX may have multiple roles affecting both extra- and intracellular cell function(s). Particularly noteworthy is aberrant LOX expression and activity that have been observed in various cancerous tissues and neoplastic cell lines. Both down and upregulation of LOX in tumor tissues and cancer cell lines have been described, suggesting a dual role for LOX as a tumor suppressor, as well as a metastasis promoter gene,creating a conundrum within the LOX research field. Here, we review the body of evidence on LOX gene expression, regulation, and function(s) in various cancer cell types and tissues, as well as stromal,tumor cell interactions. Lastly, we will examine putative mechanisms in which LOX facilitates breast cancer invasion and metastasis. Taken together, the literature demonstrates the increasingly important role(s) that LOX may play in regulating tumor progression and the necessity to elucidate its myriad mechanisms of action in order to identify potentially novel therapeutics. J. Cell. Biochem. 101: 1338,1354, 2007. © 2007 Wiley-Liss, Inc. [source] Endogenous melatonin protects L -DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long-term L -DOPA therapy in Parkinson's diseaseJOURNAL OF PINEAL RESEARCH, Issue 3 2006Gaia Rocchitta Abstract:, We previously showed, using microdialysis, that autoxidation of exogenous L-dihydroxyphenylalanine (l -DOPA) occurs in vivo in the extracellular compartment of the freely moving rat, with a consequent formation of l -DOPA semiquinone (l -DOPA-SQ). In the present study, intrastriatal infusion of l -DOPA (1.0 ,m for 200 min) increased dialysate l -DOPA concentrations (maximum increases up to 116-fold baseline values); moreover, l -DOPA-SQ was detected in dialysates. Individual dialysate concentrations of l -DOPA were negatively correlated with those of l -DOPA-SQ. Co-infusion of N -acetylcysteine (100 ,m) or melatonin (50 ,m) increased l -DOPA (up to 151- and 246-fold, respectively) and decreased l -DOPA-SQ (by about 53% and 87%, respectively) dialysate concentrations. Systemic l -DOPA [25 mg/kg intraperitoneally (i.p.) twice in a 12-h interval] significantly increased striatal baseline dialysate concentrations of l -DOPA and decreased dopamine (DA) and ascorbic acid (AsAc) concentrations, when compared with controls. Following systemic l -DOPA, l -DOPA-SQ was detected in dialysates. Endogenous melatonin was depleted in rats maintained on a 24-h light cycle for 1 wk. In melatonin-depleted rats, systemic l -DOPA induced a smaller increase in dialysate l -DOPA, a greater increase in l -DOPA-SQ formation, and a greater reduction in DA and AsAc dialysate concentrations. Co-administration of melatonin (5.0 mg/kg, i.p., twice in a 12-h interval) with l -DOPA, in control as well as in light-exposed rats, significantly increased dialysate l -DOPA concentrations, greatly inhibited l -DOPA-SQ formation, and restored up to the control values dialysate DA and AsAc concentrations. These findings demonstrate that endogenous melatonin protects exogenous l -DOPA from autoxidation in the extracellular compartment of the striatum of freely moving rats; moreover, systemic co-administration of melatonin with l -DOPA markedly increases striatal l -DOPA bioavailability in control as well as in melatonin-depleted rats. These results may be of relevance to the long-term l -DOPA therapy of Parkinson's disease. [source] dUTP Pyrophosphatase, its appearance in extracellular compartment may serve as a potential biomarker for N -methyl- N' -nitro- N -nitrosoguanidine exposure in mammalian cellsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 10 2006Meiping Wu Abstract The monofunctional alkylating agent N -methyl- N' -nitro- N -nitrosoguanidine (MNNG) is a model chemical widely used for studying the molecular events induced by the widespread environmental N -nitroso alkylating carcinogen. Many studies have focused on understanding MNNG-induced mutagenesis and carcinogenesis. However, the search for specific indicators of MNNG exposure is still underway. In this study, we analyzed the proteins in culture medium of human amnion epithelial cells (FL,cells) exposed to MNNG by 2-DE followed by MALDI-TOF,MS, in the hope of finding a specific protein marker suitable for MNNG risk assessment. Image visualization and statistical analysis indicated that 12,spots appeared and 4,spots up-regulated after MNNG exposure. Most of them were identified by MS. These proteins include nuclear isoform of dUTP pyrophosphatase (DUT-N), phosphoglycerate mutase,1, heparan sulfate proteoglycan perlecan, etc., which are involved in multiple cellular functions. Interestingly, 2-DE and MS analyses of cell lysate exposed to MNNG revealed that DUT-N was down-regulated. The appearance of DUT-N in culture medium and its down-regulation in cell lysate was confirmed by Western blot. These data suggest that these proteins, especially DUT-N, could be used as candidate biomarkers for monitoring MNNG exposure. [source] Model-Based Analysis of Potassium Removal During HemodialysisARTIFICIAL ORGANS, Issue 10 2009Andrea Ciandrini Abstract Potassium ion (K+) kinetics in intra- and extracellular compartments during dialysis was studied by means of a double-pool computer model, which included potassium-dependent active transport (Na-K-ATPase pump) in 38 patients undergoing chronic hemodialysis. Each patient was treated for 2 weeks with a constant K+ dialysate concentration (K+CONST therapy) and afterward for 2 weeks with a time-varying (profiled) K+ dialysate concentration (K+PROF therapy). The two therapies induced different levels of K+ plasma concentration (K+CONST: 3.71 ± 0.88 mmol/L vs. K+PROF: 3.97 ± 0.64 mmol/L, time-averaged values, P < 0.01). The computer model was tuned to accurately fit plasmatic K+ measured in the course and 1 h after K+CONST and K+PROF therapies and was then used to simulate the kinetics of intra- and extracellular K+. Model-based analysis showed that almost all the K+ removal in the first 90 min of dialysis was derived from the extracellular compartment. The different K+ time course in the dialysate and the consequently different Na-K pump activity resulted in a different sharing of removed potassium mass at the end of dialysis: 56% ± 17% from the extracellular compartment in K+PROF versus 41% ± 14% in K+CONST. At the end of both therapies, the K+ distribution was largely unbalanced, and, in the next 3 h, K+ continued to flow in the extracellular space (about 24 mmol). After rebalancing, about 80% of the K+ mass that was removed derived from the intracellular compartment. In conclusion, the Na-K pump plays a major role in K+ apportionment between extracellular and intracellular compartments, and potassium dialysate concentration strongly influences pump activity. [source] Mechanistic hypotheses for nonsynaptic epileptiform activity induction and its transition from the interictal to ictal state,Computational simulationEPILEPSIA, Issue 11 2008Antônio-Carlos G. De Almeida Summary Purpose:, The aim of this work is to study, by means of computational simulations, the induction and sustaining of nonsynaptic epileptiform activity. Methods:, The computational model consists of a network of cellular bodies of neurons and glial cells connected to a three-dimensional (3D) network of juxtaposed extracellular compartments. The extracellular electrodiffusion calculation was used to simulate the extracellular potential. Each cellular body was represented in terms of the transmembrane ionic transports (Na+/K+ pumps, ionic channels, and cotransport mechanisms), the intercellular electrodiffusion through gap-junctions, and the neuronal interaction by electric field and the variation of cellular volume. Results:, The computational model allows simulating the nonsynaptic epileptiform activity and the extracellular potential captured the main feature of the experimental measurements. The simulations of the concomitant ionic fluxes and concentrations can be used to propose the basic mechanisms involved in the induction and sustaining of the activities. Discussion:, The simulations suggest: The bursting induction is mediated by the Cl, Nernst potential overcoming the transmembrane potential in response to the extracellular [K+] increase. The burst onset is characterized by a critical point defined by the instant when the Na+ influx through its permeable ionic channels overcomes the Na+/K+ pump electrogenic current. The burst finalization is defined by another critical point, when the electrogenic current of the Na+/K+ pump overcomes its influx through the channels. [source] Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell linesINTERNATIONAL JOURNAL OF CANCER, Issue 10 2009Shailesh Singh Abstract Chemokines and chemokine receptors have been shown to be involved in metastatic process of prostate cancer (PCa). In this study, we show primary PCa tissues and cell lines (LNCaP and PC3) express CXCR5, a specific chemokine receptor for CXCL13. Expression of CXCR5 was significantly higher (p < 0.001) in PCa cases than compared to normal match (NM) tissues. CXCR5 intensity correlated (R2 = 0.97) with Gleason score. While prostate tumor tissues with Gleason scores , 7, displayed predominantly nuclear CXCR5 expression patterns, PCa specimens with Gleason scores , 6 showed predominantly membrane and cytoplasmic expression patterns that were comparable to benign prostatic hyperplasia (BPH). Similar to tissue expression, PCa cell lines expressed significantly more CXCR5 than normal prostatic epithelial cells (PrECs), and CXCR5 expression was distributed among intracellular and extracellular compartments. Functional in vitro assays showed higher migratory and invasive potentials toward CXCL13, an effect that was mediated by CXCR5. In both PCa cell lines, CXCL13 treatment increased the expression of collagenase-1 or matrix metalloproteinase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromelysin-2 (MMP-10) and stromelysin-3 (MMP-11). These data demonstrate the clinical and biological relevance of the CXCL13-CXCR5 pathway and its role in PCa cell invasion and migration. © 2009 UICC [source] Effect of aqueous cigarette smoke extract on the chemiluminescence kinetics of polymorphonuclear leukocytes and on their glycolytic and phagocytic activityLUMINESCENCE: THE JOURNAL OF BIOLOGICAL AND CHEMICAL LUMINESCENCE, Issue 5 2001Bruno Zappacosta Abstract Water-soluble extracts of cigarette smoke are easily formed in some body compartments, such as saliva or fluid lining alveolar spaces, and can act on both cellular and extracellular compartments. In this paper we have analysed the effect of aqueous smoke extract on some metabolic and functional aspects of polymorphonuclear leukocytes. In particular, the following cellular aspects were studied: chemiluminescence, glycolysis, membrane fluidity and microscopic interaction with zymosan particles. While chemiluminescence and glycolytic activity are highly inhibited, no effect of smoke extract on membrane fluidity was observed. Moreover, the response of luminol-dependent chemiluminescence was significantly delayed, while that of lucigenin-dependent chemiluminescence was anticipated. Furthermore, the phagocytic ability of neutrophils pretreated with aqueous smoke extract was also significantly hindered. All these results might indicate that the finely tuned activity of polymorphonuclear leukocytes is somehow hampered by the aqueous extract of cigarette smoke in a way which makes these cells less effective against bacteria and more noxious towards surrounding tissues. Copyright © 2001 John Wiley & Sons, Ltd. [source] The organic cation transporters (OCT1, OCT2, EMT) and the plasma membrane monoamine transporter (PMAT) show differential distribution and cyclic expression pattern in human endometrium and early pregnancy deciduaMOLECULAR REPRODUCTION & DEVELOPMENT, Issue 10 2007Barbara Bottalico Abstract The non-neuronal monoamine transporters (OCT1, OCT2, EMT, and PMAT) play a key role in the clearance of monoamines from extracellular compartments. In a previous report we described endometrial distribution and cyclic variation of the vesicular monoamine transporter (VMAT2) mRNA and the neuronal norepinephrine transporter (NET) mRNA. In the present study we used in situ hybridization, real-time PCR and immunohistochemistry to reveal tissue distribution and cyclic variation of mRNA for the non-neuronal monoamine transporters in the human endometrium and early pregnancy decidua. We found that non-neuronal monoamine transporters are predominantly expressed in the stroma. The plasma membrane monoamine transporter (PMAT) mRNA expression peaked in the proliferative phase, whereas the extra-neuronal monoamine transporter (EMT) mRNA expression peaked in the secretory phase. The organic cation transporter 2 (OCT2) mRNA expression was exclusively detected in few scattered stromal cells and OCT1 mRNA was not detected at all. Our present results demonstrate that PMAT, EMT, and OCT2 transporters are expressed in the endometrial stroma and can potentially regulate reuptake of monoamines in general and histamine in particular. Taken together with our previous finding of VMAT2 mRNA in epithelial cells, we suggest a paracrine interaction between stromal and epithelial cells, which may modulate certain steps of the reproductive process. Mol. Reprod. Dev. 74: 1303,1311, 2007. © 2007 Wiley-Liss, Inc. [source] Modulation of gene expression by extracellular pH variations in human fibroblasts: A transcriptomic and proteomic studyPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2003Maja A. Bumke Abstract Homeostasis of the intracellular ionic concentration, in particular that of hydrogen ions, is pivotal to the maintenance of cell function and viability. Nonetheless, pH fluctuations in both the intracellular and the extracellular compartments can occurr during development, in physiological processes and in disease. The influence of pH variations on gene expression has been studied in different model systems, but only for a limited number of genes. We have performed a broad range analysis of the patterns of gene expression in normal human dermal fibroblasts at two different pH values (in the presence and in the absence of serum), with the aim of getting a deeper insight into the regulation of the transcriptional program as a response to a pH change. Using the Affymetrix gene chip system, we found that the expression of 2068 genes (out of 12,565) was modulated by more than two-fold at 24, 48 or 72 h after the shift of the culture medium pH to a more acidic value, stanniocalcin 1 being a remarkable example of a strongly up-regulated gene. Genes displaying a modulated pattern of expression included, among others, cell cycle regulators (consistent with the observation that acidic pH abolishes the growth of fibroblasts in culture) and relevant extracellular matrix (ECM) components. Extracellular matrix protein 2, a protein with a restricted pattern of expression in adult human tissues, was found to be remarkably overexpressed as a consequence of serum starvation. Since ECM components, whose expression is controlled by pH, have been used as targets for biomolecular intervention, we have complemented the Affymetrix analysis with a two-dimensional polyacrylamide gel electrophoresis analysis of proteins which are differentially secreted by fibroblasts at acidic or basic pH. Mass spectrometric analysis of more than 650 protein spots allowed the identification of 170 protein isoforms or fragments, belonging to 40 different proteins. Some proteins were only expressed at basic pH (including, for instance, tetranectin), while others (e.g., agrin) were only detectable at acidic pH. Some of the identified proteins may represent promising candidate targets for biomedical applications, e.g., for antibody-mediated vascular targeting strategies. [source] Model-Based Analysis of Potassium Removal During HemodialysisARTIFICIAL ORGANS, Issue 10 2009Andrea Ciandrini Abstract Potassium ion (K+) kinetics in intra- and extracellular compartments during dialysis was studied by means of a double-pool computer model, which included potassium-dependent active transport (Na-K-ATPase pump) in 38 patients undergoing chronic hemodialysis. Each patient was treated for 2 weeks with a constant K+ dialysate concentration (K+CONST therapy) and afterward for 2 weeks with a time-varying (profiled) K+ dialysate concentration (K+PROF therapy). The two therapies induced different levels of K+ plasma concentration (K+CONST: 3.71 ± 0.88 mmol/L vs. K+PROF: 3.97 ± 0.64 mmol/L, time-averaged values, P < 0.01). The computer model was tuned to accurately fit plasmatic K+ measured in the course and 1 h after K+CONST and K+PROF therapies and was then used to simulate the kinetics of intra- and extracellular K+. Model-based analysis showed that almost all the K+ removal in the first 90 min of dialysis was derived from the extracellular compartment. The different K+ time course in the dialysate and the consequently different Na-K pump activity resulted in a different sharing of removed potassium mass at the end of dialysis: 56% ± 17% from the extracellular compartment in K+PROF versus 41% ± 14% in K+CONST. At the end of both therapies, the K+ distribution was largely unbalanced, and, in the next 3 h, K+ continued to flow in the extracellular space (about 24 mmol). After rebalancing, about 80% of the K+ mass that was removed derived from the intracellular compartment. In conclusion, the Na-K pump plays a major role in K+ apportionment between extracellular and intracellular compartments, and potassium dialysate concentration strongly influences pump activity. [source] Protein Targets of Oxidative Damage in Human Neurodegenerative Diseases with Abnormal Protein AggregatesBRAIN PATHOLOGY, Issue 2 2010Anna Martínez Abstract Human neurodegenerative diseases with abnormal protein aggregates are associated with aberrant post-translational modifications, solubility, aggregation and fibril formation of selected proteins which cannot be degraded by cytosolic proteases, ubiquitin,protesome system and autophagy, and, therefore, accumulate in cells and extracellular compartments as residual debris. In addition to the accumulation of "primary" proteins, several other mechanisms are involved in the degenerative process and probably may explain crucial aspects such as the timing, selective cellular vulnerability and progression of the disease in particular individuals. One of these mechanisms is oxidative stress, which occurs in the vast majority of, if not all, degenerative diseases of the nervous system. The present review covers most of the protein targets that have been recognized as modified proteins mainly using bidimensional gel electrophoresis, Western blotting with oxidative and nitrosative markers, and identified by mass spectrometry in Alzheimer disease; certain tauopathies such as progressive supranuclear palsy, Pick disease, argyrophilic grain disease and frontotemporal lobar degeneration linked to mutations in tau protein, for example, FTLD-tau, Parkinson disease and related ,-synucleinopathies; Huntington disease; and amyotrophic lateral sclerosis, together with related animal and cellular models. Vulnerable proteins can be mostly grouped in defined metabolic pathways covering glycolysis and energy metabolism, cytoskeletal, chaperoning, cellular stress responses, and members of the ubiquitin,proteasome system. Available information points to the fact that vital metabolic pathways are hampered by protein oxidative damage in several human degenerative diseases and that oxidative damage occurs at very early stages of the disease. Yet parallel functional studies are limited and further work is needed to document whether protein oxidation results in loss of activity and impaired performance. A better understanding of proteins susceptible to oxidation and nitration may serve to define damaged metabolic networks at early stages of disease and to advance therapeutic interventions to attenuate disease progression. [source] | ||||||||||||||||