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PubMed1989

Correlation of intracellular and extracellular calcium ion concentrations with synergy between 1,2-dioctanoyl-sn-glycerol and ionomycin in platelet arachidonic acid mobilization.

The potentiation by 1,2-dioctanoyl-sn-glycerol (DiC8) of ionomycin-induced platelet production of 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) was investigated in correlation with extracellular Ca2+ concentrations and increases in [Ca2+]i, as detected with aequorin and fura-2. Extracellular Ca2+ concentrations greatly influenced the production of arachidonic acid metabolites induced by DiC8 and ionomycin, while that induced by ionomycin alone was minimally affected by variation of the extracellular Ca2+ concentration. In the synergy between ionomycin and 20 microM DiC8, the optimal concentrations of ionomycin shifted from high to low with increasing concentrations of extracellular Ca2+, suggesting that there might be a range of optimal [Ca2+]i for the production of the arachidonic acid metabolites. This hypothesis was confirmed by simultaneous measurements of [Ca2+]i increases, and the production of the arachidonic acid metabolites. With the aequorin method, the optimal concentrations of [Ca2+]i fell to between 10 microM and 20 microM, and with the fura-2 method, it fell to between 800 nM and 1800 nM. Direct measurements of [14C]arachidonic acid release suggested that the DiC8-potentiated production of arachidonic acid metabolites induced by ionomycin was attributable to increased arachidonic acid release. Since ionomycin and DiC8 induced relatively low levels of phosphatidic acid production, an indicator of phospholipase C activation, it was suggested that the increased arachidonic acid release was largely dependent upon phospholipase A2. Synergy between DiC8 and ionomycin was also observed with aggregation and serotonin release. Aggregation was induced by lower concentrations of ionomycin, and appeared to be more dependent upon extracellular Ca2+, while serotonin release required higher concentrations of ionomycin, and variations in extracellular Ca2+ affected the response minimally. These findings suggest that the mechanisms underlying the synergy between protein kinase C activation and Ca2+ mobilization differ among the three functions evaluated in this study.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed2004

In vivo posttranslational modifications of the high mobility group A1a proteins in breast cancer cells of differing metastatic potential.

The high mobility group (HMG) proteins are important modulators of chromatin structure and gene transcription. Overexpression of HMGA1 proteins in vivo induces neoplastic transformation and promotes a highly metastatic cellular phenotype. This study focuses on characterization of HMGA1a in vivo posttranslational modification (PTM) patterns found in a nonmetastatic and two metastatic lines of MCF-7 human breast cancer cells of differing tumorigenic potential. PTM types and the amino acids on which they occur were identified by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. Mass analysis was restricted to MALDI peaks having less than +/-150 parts per million (ppm) error, thereby holding our analysis to a more stringent criterion than previously published work with the HMG proteins. Validation of MALDI-TOF MS analysis was accomplished utilizing electrospray ionization tandem mass spectrometry (ESI MS/MS) and manual analysis of ion fragmentation spectra. Patterns and sites of PTMs identified in this study suggest that HMGA1a proteins, like the histones, exhibit a biochemical modification "code" that relates to cellular function. For example, both increased levels of acetylation and a previously unidentified dimethylation of both lysine and arginine residues were found on HMGA1a proteins from metastatic cells compared to proteins found in their nonmetastatic precursors. Additionally, the types of modification present on lysine-45 (e.g., unmodified, acetylation, or dimethylation) varied, depending on the metastatic potential of cells. These findings suggest that examination of the PTM patterns on HMGA1 proteins may provide valuable information concerning the physiological and phenotypic state of mammalian cells.

Amino Acid Sequence↗
PubMed2006

Placental growth factor-1 potentiates hematopoietic progenitor cell mobilization induced by granulocyte colony-stimulating factor in mice and nonhuman primates.

The complex hematopoietic effects of placental growth factor (PlGF) prompted us to test in mice and nonhuman primates the mobilization of peripheral blood progenitor cells (PBPCs) elicited by recombinant mouse PlGF-2 (rmPlGF-2) and recombinant human PlGF-1 (rhPlGF-1). PBPC mobilization was evaluated by assaying colony-forming cells (CFCs), high-proliferative potential-CFCs (HPP-CFCs), and long-term culture-initiating cells (LTC-ICs). In mice, both rmPlGF-2 and rhPlGF-1 used as single agents failed to mobilize PBPCs, whereas the combination of rhPlGF-1 and granulocyte colony-stimulating factor (rhG-CSF) increased CFCs and LTC-ICs per milliliter of blood by four- and eightfold, respectively, as compared with rhG-CSF alone. rhPlGF-1 plus rhG-CSF significantly increased matrix metalloproteinase-9 plasma levels over rhG-CSF alone, suggesting a mechanistic explanation for rhPlGF-1/rhG-CSF synergism. In rhesus monkeys, rhPlGF-1 alone had no mobilization effect, whereas rhPlGF-1 (260 microg/kg per day) plus rhG-CSF (100 microg/kg per day) increased rhG-CSF-elicited mobilization of CFCs, HPP-CFCs, and LTC-ICs per milliliter of blood by 5-, 7-, and 15-fold, respectively. No specific toxicity was associated with the administration of rhPlGF-1 alone or in combination. In conclusion, our data demonstrate that rhPlGF-1 significantly increases rhG-CSF-elicited hematopoietic mobilization and provide a preclinical rationale for evaluating rhPlGF-1 in the clinical setting.

Animals↗
PubMed2002

The antidepressant-like effect induced by the sigma(1) (sigma(1)) receptor agonist igmesine involves modulation of intracellular calcium mobilization.

RATIONALE: Activation of the neuronal sigma(1) (sigma(1)) receptor potentiates calcium mobilization, leading to effective modulation of postsynaptic responses to neurotransmitters. At the behavioral level, sigma(1) agonists modulate learning, response to stress and depression. In particular, the selective sigma(1) agonist igmesine reduced immobility in the forced swimming test. OBJECTIVES AND METHODS: We investigated the effect of modulators of Ca(2+) influx and mobilization, administered intracerebroventricularly at doses ineffective alone, on the igmesine effect. The tricyclic antidepressant desipramine was also studied for comparison. RESULTS: The calcium chelator EGTA blocked both igmesine and desipramine-induced decreases of immobility duration, indicating the importance of extracellular Ca(2+) influx in the initial action of each compound. Both L- and N-type voltage-dependent calcium channel (VDCC) appeared involved in the sigma(1) agonist effect. Verapamil, an L-type VDCC antagonist or omega-conotoxin GVI, a N-type VDCC antagonist, blocked whereas (-)-Bay K8644, a L-type VDCC agonist, potentiated the igmesine effect. Mobilization of intracellular Ca(2+) stores is involved selectively in the effect mediated by the sigma(1) receptor, since the membrane permeable intracellular Ca(2+) chelator EGTA/AM affected only the igmesine effect. Inositol 1,4,5-trisphosphate (InsP(3)) receptor-sensitive Ca(2+) pools appeared primarily involved, rather than Ca(2+)/caffeine-sensitive Ca(2+) pools. Indeed, the InsP(3) receptor positive modulator bradykinin potentiated, whereas the InsP(3) receptor antagonist xestospongin C blocked the igmesine effect. The ryanodine receptor agonist caffeine failed to affect the efficacy of igmesine, whereas the antagonist ryanodine reduced it. CONCLUSIONS: The sigma(1) receptor-mediated behavioral effect is dependent not only on rapid Ca(2+) influx, as observed for a classical antidepressant, but also on intracellular Ca(2+) mobilization.

Adrenalectomy↗
PubMed2004

Microbial acidification and pH effects on trace element release from sewage sludge.

Leaching of sludge-borne trace elements has been observed in experimental and field studies. The role of microbial processes in the mobilization of trace elements from wastewater sludge is poorly defined. Our objectives were to determine trace element mobilization from sludge subjected to treatments representing microbial acidification, direct chemical acidification and no acidification, and to determine the readsorption potential of mobilized elements using calcareous sand. Triplicate columns (10-cm diameter) for incubation and leaching of sludge had a top layer of digested dewatered sludge (either untreated, acidified with H2SO4, or limed with CaCO3; all mixed with glass beads to prevent ponding) and a lower glass bead support bed. Glass beads in the sludge layer, support layer or both were replaced by calcareous sand in four treatments used for testing the readsorption potential of mobilized elements. Eight sequential 8-day incubation and leaching cycles were operated, each consisting of 7.6 d of incubation at 28 degrees C followed by 8 h of leaching with synthetic acid rain applied at 0.25 cm/h. Leachates were analyzed for trace elements, nitrate and pH, and sludge layer microbial respiration was measured. The largest trace element, nitrate and S losses occurred in treatments with the greatest pH depression and greatest microbial respiration rates. Cumulative leaching losses from both microbial acidification and direct acidification treatments were > 90% of Zn and 64-80% of Cu and Ni. Preventing acidification with sludge layer lime or sand restricted leaching for all trace elements except Mo. Results suggested that the primary microbial role in the rapid leaching of trace elements was acidification, with results from direct acidification being nearly identical to microbial acidification. Microbial activity in the presence of materials that prevented acidification mobilized far lower concentrations of trace elements, with the exception of Mo. Trace elements mobilized by acidification were readsorbed by calcareous sand when present.

Calcium↗
PubMed1999

A Comparison of Streaming and Microelectrophoresis Methods for Obtaining the zeta Potential of Granular Porous Media Surfaces.

The electrokinetic behavior of granular quartz sand in aqueous solution is investigated by both microelectrophoresis and streaming potential methods. zeta potentials of surfaces composed of granular quartz obtained via streaming potential methods are compared to electrophoretic mobility zeta potential values of colloid-sized quartz fragments. The zeta values generated by these alternate methods are in close agreement over a wide pH range and electrolyte concentrations spanning several orders of magnitude. Streaming measurements performed on chemically heterogeneous mixtures of physically homogeneous sand are shown to obey a simple mixing model based on the surface area-weighted average of the streaming potentials associated with the individual end members. These experimental results support the applicability of the streaming potential method as a means of determining the zeta potential of granular porous media surfaces. Copyright 1999 Academic Press.

Journal Article↗
PubMed1990

Effect of inhibition of Na+/K(+)-adenosine triphosphatase on vascular action of vasopressin.

The present study was undertaken to examine the cellular interaction between a Na+/K(+)-ATPase inhibitor, ouabain, and arginine vasopressin (AVP) in rat vascular smooth muscle cells (VSMC) in culture. Preincubation with 10(-5) M ouabain for 60 min increased basal cytosolic free Ca2+ [( Ca2+]i) concentration and intracellular 45Ca2+ uptake. Ouabain, however, did not affect basal 45Ca2+ efflux or AVP-stimulated 45Ca2+ efflux. As assessed by cell shape change, preincubation with 10(-5) M ouabain for 60 min also enhanced the sustained cellular contractile effect of a submaximal (10(-8) M AVP, 21.5% vs. 30.5%, P less than 0.01) but not maximal dose of 10(-6) M AVP. Preincubation with 10(-5) M ouabain for 60 min did not change AVP-induced V1-specific surface receptor binding or AVP-induced inositol phosphate production but did however potentiate the mobilization of [Ca2+]i induced by a submaximal (10(-8) M AVP, 301 vs. 385 nM, P less than 0.01) but not a maximal dose of AVP. These effects of ouabain on the mobilization of [Ca2+]i were abolished by incubation in Ca2(+)-free buffer or 5 X 10(-5) M verapamil. Ouabain (10(-5) M) also enhanced the sustained cellular contractile effect of a direct protein kinase C activator, phorbol 12-myristate 13-acetate. The present results therefore indicate that the inhibition of Na+/K(+)-ATPase may enhance the vascular action of AVP, and perhaps other vasoconstrictors, by increasing the AVP-induced mobilization of [Ca2+]i and by potentiating the activity of protein kinase C stimulated by AVP through enhancing basal and AVP-stimulated cellular Ca2+ uptake.

Animals↗
PubMed2003

No effects of acute exposure to the electromagnetic field emitted by mobile phones on brainstem auditory potentials in young volunteers.

OBJECTIVES: A widespread use of mobile phones evokes a growing concern for their possible adverse effects on the human central nervous system. This study was aimed at evaluating the effects of EMF generated by mobile phones, at all standard wavelengths: 450, 935 and 1800 MHz used in Poland, on the auditory brainstem-evoked responses (ABR) during and after the exposure. MATERIALS AND METHODS: The effects of acute exposure to electromagnetic fields (EMF) on ABR were evaluated in 45 young, healthy volunteers of both genders. The electromagnetic impulses were generated with the antenna of mobile phone. The exposure was induced by repeated phone activation for 20 min. The ABR evaluation was performed before, during and immediately after the exposure, and the latencies of waves I, III and V, and inter-waves I-V were analyzed. RESULTS: Prior test calibration on a phantom did not show the influence of the external EMF generated by the mobile phone on the ABR equipment. For neither EMF frequency, differences were observed in wave and inter-wave latencies during and after exposure to EMF compared to the initial ABR pattern, in both men and woman. CONCLUSIONS: This implies that commonly used mobile phones do not affect propagation of electrical stimuli along the auditory nerve to auditory brainstem centers.

Adult↗
PubMed2006

M-score: a knowledge-based potential scoring function accounting for protein atom mobility.

A knowledge-based potential scoring function, named M-Score, has been developed based upon 2331 high-resolution crystal structures of protein-ligand complexes. M-Score considers the mobility of protein atoms, describing the location of each protein atom by a Gaussian distribution instead of a fixed position based upon the isotropic B-factors. This leads to an increase in the number of atom-pairs in the construction of knowledge-based potentials and a smoothing effect on the pairwise distribution functions. M-Score was validated using 896 complexes which were not included in the 2331 data set and whose experimentally determined binding affinities were available. The overall linear correlation coefficient (r) between the calculated scores and experimentally determined binding affinities (pKi or pKd) for these 896 complexes is -0.49. Evaluation of M-Score against 17 protein families showed that we obtained good to excellent correlations for six protein families, modest correlations for four protein families, and poor correlations for the remaining seven protein families.

Algorithms↗
PubMed2003

Potentiation of intracellular Ca2+ mobilization by hypoxia-induced NO generation in rat brain striatal slices and human astrocytoma U-373 MG cells and its involvement in tissue damage.

The relationship between nitric oxide (NO) and intracellular Ca2+ in hypoxic-ischemic brain damage is not known in detail. Here we used rat striatal slices perfused under low-oxygen and Ca2+-free conditions and cultured human astrocytoma cells incubated under similar conditions as models to study the dynamics of intracellular NO and Ca2+ in hypoxia-induced tissue damage. Exposure of rat striatal slices for 70 min to low oxygen tension elicited a delayed and sustained increase in the release of 45Ca2+. This was potentiated by the NO donors sodium nitroprusside (SNP) and spermine-NO and inhibited by N-omega-nitro-L-arginine methyl ester (L-NAME) or by the NO scavenger 2-phenyl-4,4,5,5 tetramethylimidazoline-1-oxyl-3-oxide (PTIO). A membrane-permeant form of heparin in combination with either ruthenium red (RR) or ryanodine (RY) also inhibited 45Ca2+ release. In human astrocytoma U-373 MG cells, hypoxia increased intracellular Ca2+ concentration ([Ca2+]i) by 67.2 +/- 13.1% compared to normoxic controls and this effect was inhibited by L-NAME, PTIO or heparin plus RR. In striatal tissue, hypoxia increased NO production and LDH release and both effects were antagonized by L-NAME. Although heparin plus RR or RY antagonized hypoxia-induced increase in LDH release they failed to counteract increased NO production. These data therefore indicate that NO contributes to hypoxic damage through increased intracellular Ca2+ mobilization from endoplasmic reticulum and suggest that the NO-Ca2+ signalling might be a potential therapeutic target in hypoxia-induced neuronal degeneration.

Animals↗
PubMed1997

Electrophoretic Mobility of a Semi-dilute Suspension of Spherical Particles with Thick Double Layers and Low Zeta Potentials

The electrophoretic mobilities of two spherical particles are analyzed for the case where the electrical double layer is no longer thin with respect to the particle sizes, but the zeta potentials on the particles are low. Using a method of reflections, we obtain the mobilities as a power series in 1/r12 up to O(r-1012) (where r12 is the center-to-center separation of the spheres), with the proviso that the double layers on the two particles do not overlap. Unlike the case of thin double layers, there is now a nonzero interaction between identical particles. The first term in the interaction is O(r-312), but the coefficient becomes large for thick double layers. An expression for the average mobility of a mildly polydisperse suspension of spheres with thick double layers is then derived correct to first order in the volume fraction of the spheres. The results of the reflection calculation are then used to obtain an approximate evaluation of this expression. It is found that the first order effect for thick double layers is significantly larger than it is for thin double layers, and that the average effect of polydispersity in size or surface potential is weak unless the double layers are quite thick. For a monodisperse suspension, an expression is obtained for the mean square deviation of the particle velocity from the mean velocity. An approximate evaluation of this expression using the reflection results shows that the magnitude of the mean square fluctuations in the direction of the applied field can be significantly larger than that in the transverse direction.

Journal Article↗
PubMed1998

Is screening for abdominal aortic aneurysm acceptable to the population? Selection and recruitment to hospital-based mass screening for abdominal aortic aneurysm.

BACKGROUND: The aim of the study was to analyse whether the selection and recruitment for hospital-based mass screening for abdominal aortic aneurysms (AAA) is acceptable for the population according to the criteria from the Council of Europe. METHODS: A random sample of 4404 65-73-year-old males were invited to hospital-based mass screening for AAA. As methods of secondary recruitment, they could change their time of appointment, and non-responders were reinvited once. RESULTS: The attendance rate was 76 per cent; 4.2 per cent had AAA. Men with cardiopulmonary and vascular diseases had higher attendance rate (80.5 per cent), and prevalence of AAA (9.1 per cent). Men with potentially mobility-disabling diseases also had a higher attendance rate (80.4 per cent). However, possible unfavourable social selection was noticed in the group of retired men with no information of former occupation. They had 68.5 per cent attendance, and 7.6 per cent AAA. If true, this selection decreases the number of potentially diagnosed AAA by only 2 per cent. Opportunity of revised appointment and reinvitation of non-responders increased the primary attendance of 65 per cent to 76 per cent. More AAA were found at secondary scans (6.3 per cent compared with 3.9 per cent). CONCLUSION: The attendance rate fell markedly with age, but the recruitment was high even at the age of 73, and travel distance and social class did not markedly influence uptake. A positive morbidity selection to screening for AAA was observed for cardiovascular or pulmonary diseases and potentially mobility-disabling diseases. Furthermore, higher prevalence of AAA was found for initial nonattenders. Thus, screening for AAA seems acceptable to the population, and extra efforts to increase the attendance are beneficial without increased costs per diagnosed AAA. Finally, if mass-screening proves to be cost-ineffective, selective screening of patients with hypertension or ischaemic heart disease might be beneficial.

Age Distribution↗
PubMed1998

CD34+ cells mobilized by cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) are functionally different from CD34+ cells mobilized by G-CSF.

Mobilized peripheral blood progenitor cells (PBPC) are increasingly used as an alternative to bone marrow for autografting procedures. Currently, cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF) or G-CSF alone are the most commonly used PBPC mobilization schedules. In an attempt to investigate whether the use of these two mobilization regimens could result in the collection of functionally different CD34+ cells, we analyzed nucleated cells (NC), CD34+ cells, committed progenitor cells and long-term culture initiating-cells (LTC-IC) in 52 leukaphereses from 26 patients with lymphoid malignancies, mobilized either by CY+G-CSF (n=16) or G-CSF alone (n=10). Thirty-four aphereses from the CY+G-CSF group and 18 aphereses from the G-CSF group were investigated. According to the study design, leukaphereses were carried out until an average number of 7 x 10(6) CD34+ cells/kg body weight were collected. The mean (+/-s.e.m.) numbers of CD34+ cells mobilized per apheresis by CY+G-CSF and G-CSF were not significantly different (2.76+/-0.6 x 10(8) vs 2.53+/-0.4 x 10(8), P < or = 0.7). This resulted from a mean number of NC that was significantly lower in the CY+G-CSF products than in the G-CSF products (12.4+/-1.7 x 10(9) vs 32+/-5.4 x 10(9), P < or = 0.0001) and a mean incidence of CD34+ cells that was significantly higher in the CY+G-CSF products than in the G-CSF products (2.9+/-0.6% vs 0.9+/-0.2%, P < or = 0.0018). The mean (+/-s.e.m.) number of CFU-GM collected per apheresis was significantly higher in the CY+G-CSF group than in the G-CSF group (37+/-7 x 10(6) vs 14+/-2 x 10(6), P < or = 0.03). Interestingly, CY+G-CSF-mobilized CD34+ cells had a significantly higher plating efficiency than G-CSF-mobilized CD34+ cells (25.5+/-2.9% vs 10.8+/-1.9%, P < or = 0.0006). In addition, the mean number of LTC-IC was significantly higher in the CY+G-CSF products than in the G-CSF products (6.3+/-1 x 10[6] vs 3.3+/-0.3 x 10[6], P < or = 0.05). In conclusion, our data provide evidence that CY+G-CSF and G-CSF induce the mobilization of CD34+ cells with different clonogenic potential. As mobilized PBPC containing large numbers of progenitors lead to safer transplantation, this issue may have implications for planning mobilization strategies.

Adult↗
PubMed1982

Calcium movement and membrane potential changes in the early phase of neutrophil activation by phorbol myristate acetate: a study with ion-selective electrodes.

To quantitate calcium movements and membrane potential changes in stimulated neutrophils, we have measured net fluxes of Ca2+ and of the lipophilic cation tetraphenyl phosphonium by a very sensitive ion-selective electrode system. Activation of neutrophils by 3 X 10(-8) M phorbol 12-myristate, 13-acetate induces a release of approximately 20% of total cell calcium, with an initial lag period of less than 10 s. The Ca2+ outflux is markedly reduced in ATP-depleted cells and in the presence of a calmodulin inhibitor, thereby suggesting that it occurs by activation of the ATP-driven Ca2+ pump of the neutrophil plasmalemma. Activation of neutrophils also induces a transiently increased exchange of medium 45Ca with cell calcium, which is measurable a few seconds after cell exposure to the stimulant and peaks at approximately 40 s. Stimulation of neutrophils after attainment of steady-state accumulation of tetraphenyl phosphonium (resting potential of -67 mV) results in a marked depolarization, with a lag period of approximately 60 s. The rate and extent of depolarization are reduced by 40 and 65%, respectively, in a low Na+ medium but are not modified by an inhibitor of anion exchange across membranes. A high-K+ medium depolarizes neutrophils without either modifying their resting oxidative metabolism or impairing stimulability by the phorbol ester. Phorbol 12-myristate, which also exhibits no effect on the oxidative metabolism of neutrophils, does not induce Ca2+ extrusion and membrane potential changes. The causal relationship between Ca2+ mobilization, membrane potential changes and activation of neutrophil functions is discussed.

Animals↗
PubMed1997

CD38 and ADP-ribosyl cyclase catalyze the synthesis of a dimeric ADP-ribose that potentiates the calcium-mobilizing activity of cyclic ADP-ribose.

CD38, a lymphocyte differentiation antigen, is also a bifunctional enzyme catalyzing the synthesis of cyclic ADP-ribose (cADPR) from NAD+ and its hydrolysis to ADP-ribose (ADPR). An additional enzymatic activity of CD38 shared by monofunctional ADP-ribosyl cyclase from Aplysia californica is the exchange of the base group of NAD+ (nicotinamide) with various nucleophiles. Both human CD38 (either recombinant or purified from erythrocyte membranes) and Aplysia cyclase were found to catalyze the exchange of ADPR with the nicotinamide group of NAD+ leading to the formation of a dimeric ADPR ((ADPR)2). The dimeric structure of the enzymatic product, which was generated by recombinant CD38 and by CD38(+) Namalwa cells from as low as 10 microM NAD+, was demonstrated using specific enzyme treatments (dinucleotide pyrophosphatase and 5'-nucleotidase) and mass spectrometry analyses of the resulting products. The linkage between the two ADPR units of (ADPR)2 was identified as that between the N1 of the adenine nucleus of one ADPR unit and the anomeric carbon of the terminal ribose of the second ADPR molecule by enzymatic analyses and by comparison with patterns of cADPR cleavage with Me2SO:tert-butoxide. Although (ADPR)2 itself did not release Ca2+ from sea urchin egg microsomal vesicles, it specifically potentiated the Ca2+-releasing activity of subthreshold concentrations of cADPR. Therefore, (ADPR)2 is a new product of CD38 that amplifies the Ca2+-mobilizing activity of cADPR.

ADP-ribosyl Cyclase↗
PubMed2006

IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis.

IL-22 is an IFN-IL-10 cytokine family member, which is produced by activated Th1 and NK cells and acts primarily on epithelial cells. Here we demonstrate that IL-22, in contrast to its relative IFN-gamma, regulates the expression of only a few genes in keratinocytes. This is due to varied signal transduction. Gene expressions regulated by IL-22 should enhance antimicrobial defense [psoriasin (S100A7), calgranulin A (S100A8), calgranulin B (S100A9)], inhibit cellular differentiation (e.g., profilaggrin, keratins 1 and 10, kallikrein 7), and increase cellular mobility [e.g., matrix metalloproteinease 1 (MMP1, collagenase 1), MMP3 (stromelysin 1), desmocollin 1]. In contrast, IFN-gamma favored the expression of MHC pathway molecules, adhesion molecules, cytokines, chemokines, and their receptors. The IL-22 effects were transcriptional and either independent of protein synthesis and secretion, or mediated by a secreted protein. Inflammatory conditions, but not keratinocyte differentiation, amplified the IL-22 effects. IL-22 application in mice enhanced cutaneous S100A9 and MMP1 expression. High IL-22 levels in psoriatic skin were associated with strongly up-regulated cutaneous S100A7, S100A8, S100A9, and MMP1 expression. Psoriatic patients showed strongly elevated IL-22 plasma levels, which correlated with the disease severity. Expression of IL-22 and IL-22-regulated genes was reduced by anti-psoriatic therapy. In summary, despite similarities, IFN-gamma primarily amplifies inflammation, while IL-22 may be important in the innate immunity and reorganization of epithelia.

Animals↗
PubMed2004

[Potentialities of enhancing the diagnostic efficiency in registering the electrophoretic mobility of erythrocytes].

The potentialities of optimizing the clinical use of electric surface properties of erythrocyte blood samples were investigated. The ordinarily used parameter of the eletrokinetic erythrocyte potential based on the mean value of electrophoretic mobility was shown to be inaccurate and low informative. Asymmetry factor and erythrogram excess (distribution parameters) are recommended for use to enhance the adequate evaluation of changes in the above parameter and to make it diagnostically more effective. Principles of interpretation of changes' results are described.

Cell Movement↗