Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further understand the mechanisms involved in phagocyte activation in general and in NADPH oxidase activation in particular, a polyclonal antibody was raised in rabbit against a partially purified oxidase preparation. The enzyme was solubilized from zymosan-activated human neutrophils and resting cells and separated by preparative isoelectric focusing electrophoresis. A polyclonal antibody was raised in rabbit against the pI 5.0 fraction, which had the maximum superoxide-producing capacity. Analysis of the polyclonal antibody revealed marked differences between activated and resting neutrophils. The antibody recognized in particular an 8-kDa protein (p8) in resting human neutrophil cytosol and in the membrane of zymosan-activated cells. A polyclonal antibody (anti-p8) was raised against the pure cytosolic p8 protein. This anti-p8 reacted not only with p8, but also with cytosolic proteins of 14 kDa and 6 kDa. N-terminal amino acid sequence analysis of p8 revealed homology with the calcium-binding myeloid related protein (MRP-8). Upon neutrophil activation, translocation of the 8- and 14-kDa proteins to the membrane was observed with stimuli known to depend on extracellular calcium. In calcium-depleted medium, the absence of translocation correlated with a depression of superoxide production, supporting a role for the calcium-binding protein in cellular activation.
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PMID:Translocation of a small cytosolic calcium-binding protein (MRP-8) to plasma membrane correlates with human neutrophil activation. 132 51

The possible role of intracellular calcium on daunorubicin (DNR) accumulation in wild-type (EHR2) and multi-drug resistant (MDR) Ehrlich ascites tumor cell subline was investigated. DNR accumulation was not enhanced either by increasing the concentration of cellular calcium with the calcium ionophore ionomycin nor by chelating the cytosolic free Ca2+ by the membrane permeable Ca2(+)-buffering agents BAPTA or MAPTAM. No effect was observed in the presence of extremely low extracellular calcium concentration that prevent transmembrane calcium influx or when the cells were calcium depleted using EGTA and ionomycin. Using the fluorescent Ca2+ indicator fura-2 it is further shown that both drug-resistant daunorubicin (EHR2/DNR+) and vincristine (EHR/VCR+) sublines had lower (50-80 nM) concentration of cytosolic free calcium ([Ca2+]i) compared to their corresponding wild-type parenteral tumors (140-180 nM). In calcium free medium, however, no significant difference was found, all cell lines having a [Ca2+]i of 60-80 nM. Furthermore, the total amount of Ca2+ released to the cytosol with 10 microM ionomycin and 5 mM EGTA was 3-4-fold higher in EHR2 than in EHR2/DNR+ or EHR2/VCR+. Mobilization of Ca2+ with 1 microM ionomycin was almost identical in the presence and absence of Ca2+ in the extracellular medium in EHR2 as well as in EHR2/DNR+ suggesting that the increase in [Ca2+]i is mainly due to discharge of Ca2+ from intracellular stores. Furthermore, the total cell calcium [Ca2+]t concentration was slightly higher in EHR2/DNR+ and EHR2/VCR+ cells compared to EHR2. Incubation of the cells with the Ca2(+)-channel blocker verapamil or the intracellular Ca2(+)-antagonist TMB-8 causes depression of the Ca2(+)-response in terms of rise in [Ca2+]i caused by ionomycin. Sorcin, a major calcium-binding protein (Mr 22 kDa), is shown to be overproduced in EHR2/DNR+ cells. The overproduction of this protein in resistant cells may be related to the difference in the intracellular calcium observed in this study. Thus, though handling of Ca2+ is different in wild-type and MDR cell lines, our data suggest that calcium is not involved directly in drug transport processes and the level of Ca2+ per se have no influence on drug accumulation.
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PMID:Cytosolic free Ca2+ in daunorubicin and vincristine resistant Ehrlich ascites tumor cells. Drug accumulation is independent of intracellular Ca2+ changes. 189 93

The effect of dietary phosphorus deficiency on the performance and on various parameters of calcium, phosphorus, and vitamin D metabolism was studied in laying hens. Phosphorus deficiency resulted in a decline in rate of production and egg weight, probably through appetite depression. The latter, or any secondary calcium deficiency, does not appear to cause the observed reduction in shell quality due to the deficiency. Similar to the response in the chick, phosphorus deficiency resulted in an increase in calcium-binding protein in intestine and kidney, there was no change in the activity of kidney 25-hydroxy-vitamin D3-1-hydroxylase. Percentages of calcium and phosphorus absorption were also higher during phosphorus deficiency. Medullary bone ash, decreased during phosphorus deficiency, was probably due to a reduction in the rate of bone formation.
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PMID:Egg shell quality, medullary bone ash, intestinal calcium and phosphorus absorption, and calcium-binding protein in phosphorus-deficient hens. 654 88

Recent evidence suggests that slowly propagating Ca2+ waves from astrocytes can modulate the function of neurons. Altering astrocytic calcium processes in vivo may therefore affect neuronal and behavioral phenotypes. Previously, we generated transgenic mice that overexpress an astrocytic calcium-binding protein, S100 beta. Immunocytochemistry and in situ hybridization showed elevated expression in the astrocytes of the hippocampus and other brain regions. Neurons in the hippocampus were negative for S100 beta. In this paper we analyze the hippocampal electrophysiology and learning properties of mice from two transgenic lines. Significant differences were found between the hippocampal slices of normal and transgenic mice in their response to high frequency (100 Hz) stimulation. The overall distribution of post-tetanic excitatory postsynaptic potentials (EPSP) of the slices from the transgenic mice was shifted significantly toward smaller values to a degree that 25% of slices exhibited depression. The altered hippocampal neurophysiology was accompanied by an impairment in a hippocampal-dependent learning task. Transgenic mice showed significant impairment in a spatial version of the Morris water maze, however, they performed normally in non-spatial tasks. Probe trials showed that transgenic mice, though significantly impaired, also acquired spatial information. The results suggested that the impairment was not due to motor dysfunction, impaired vision or motivation of the transgenic mice, findings compatible with a possible hippocampal mechanism. We conclude that overexpression of S100 beta in astrocytes impairs, but does not abolish, the ability to solve a spatial task, and it leads to a significantly decreased post-tetanic potentiation in the hippocampal slice. We hypothesize that the changes are due to calcium mediated processes. Our results support the notion that astrocytes are involved in higher brain functions.
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PMID:Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice. 1046 64

Long-term depression (LTD) of Purkinje cell-parallel fiber synaptic transmission is a critical determinant of normal cerebellar function. Impairment of LTD through, for example, disruption of the metabotropic glutamate receptor-IP3-calcium signaling cascade in mutant mice results in severe deficits of both synaptic transmission and cerebellar motor control. Here, we demonstrate that selective genetic deletion of the calcium-binding protein calbindin D-28k (calbindin) from cerebellar Purkinje cells results in distinctly different cellular and behavioral alterations. These mutants display marked permanent deficits of motor coordination and sensory processing. This occurs in the absence of alterations in a form of LTD implicated in the control of behavior. Analysis of synaptically evoked calcium transients in spines and dendrites of Purkinje cells demonstrated an alteration of time course and amplitude of fast calcium transients after parallel or climbing fiber stimulation. By contrast, the delayed metabotropic glutamate receptor-mediated calcium transients were normal. Our results reveal a unique role of Purkinje cell calbindin in a specific form of motor control and suggest that rapid calcium buffering may directly control behaviorally relevant neuronal signal integration.
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PMID:Calbindin in cerebellar Purkinje cells is a critical determinant of the precision of motor coordination. 1271 55

Neuronal calcium sensor-1 (NCS-1) is a member of EF-hand calcium-binding protein superfamily, which is considered to modulate synaptic transmission and plasticity. In this mini-review, we first summarize distribution of NCS-1 in the cerebellum. NCS-1 is mainly detected in postsynaptic sites, such as somata and dendrites of Purkinje cells, stellate/basket cells and granule cells. In addition, GABAergic inhibitory stellate/basket cell axon terminals also contain NCS-1. Secondly, we describe cerebellar compartmentation defined by NCS-1. The NCS-1 immunostaining displayed characteristic parasagittal-banding pattern in the Purkinje cell layer and molecular layer, whereas there were no apparent bands in the granule cell layer. The alternating positively and negatively NCS-1-labeled Purkinje cell clusters contributed to this cerebellar compartmentation. In contrast, stellate/basket cells were uniformly NCS-1-positive throughout the cerebellum. Interestingly, NCS-1 and zebrin II exhibited a similar parasagittal-banding pattern. But it is noteworthy that NCS-1-negative/zebrin II-positive Purkinje cell clusters were detected selectively in anterior lobule vermis and paraflocculus. These results suggest that NCS-1 defines a novel pattern of cerebellar cortical compartmentation. Lastly, we describe recent data suggesting some relationship between NCS-1 and cerebellar long-term depression-related molecules, and discuss the possible role of NCS-1 in the cerebellum.
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PMID:Expression and possible role of neuronal calcium sensor-1 in the cerebellum. 1523 74

Prolonged changes in motor neurone activity can result in long-term changes in synaptic transmission. We investigated whether mechanisms commonly thought to be involved in determining synaptic efficacy of vertebrate motor neurones are involved in these long-term changes. The nerve supplying the cutaneous pectoris muscle was chronically stimulated via skin surface electrodes in freely moving frogs for 5-7 days. Chronic stimulation induced a 50% reduction in evoked endplate potential (EPP) amplitude at stimulated neuromuscular junctions (NMJs). These changes appear to be presynaptic since miniature EPP (mEPP) amplitude was unchanged while mEPP frequency was decreased by 46% and paired-pulse facilitation was increased by 26%. High frequency facilitation (40 Hz, 2 s) was also increased by 89%. Moreover, stimulated NMJs presented a 92% decrease in synaptic depression (40 Hz, 2 s). An increase in mitochondrial metabolism was observed as indicated by a more pronounced labelling of active mitochondria (Mitotracker) in stimulated nerve terminals, which could account for their greater resistance to synaptic depression. NMJ length visualized by alpha-bungarotoxin staining of nAChRs was not affected. Presynaptic calcium signals measured with Calcium Green-1 were larger in stimulated NMJs at low frequency (0.2 Hz) and not different from control NMJs at higher frequency (40 Hz, 2 s and 30 s). These results suggest that some mechanisms downstream of calcium entry are responsible for the determination of synaptic output, such as a down-regulation of some calcium-binding proteins, which could explain the observed results. The possibility of a change in frequenin expression, a calcium-binding protein that is more prominently expressed in phasic synapses, was, however, refuted by our results.
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PMID:Long-term in vivo modulation of synaptic efficacy at the neuromuscular junction of Rana pipiens frogs. 1616 59

Arundic acid (ONO-2506) is believed to be neuroprotective because of its actions on glia cells; i.e., its inhibitory effects on the synthesis of a calcium-binding protein S100B. ONO-2506 is undergoing clinical trials for the treatment of patients with stroke and Alzheimer's disease. Recent clinical studies point to a pervasive comorbidity of depression with stroke and Alzheimer's disease. Previously, S100B has been implicated in the pathobiological mechanisms of depression. Preclinical studies have shown that antidepressant treatment significantly increases brain S100B. Here we hypothesize that available data that link S100B with depression, along with the proposed inhibitory action of ONO-2506 on S100B synthesis, indicate that this compound could increase vulnerability for depression in patients at risk for this disorder, and we propose that evaluation of patients with stroke and Alzheimer's disease for the presence of depression should be routine in clinical trials employing ONO-2506. Although it may be open for discussion whether the neuroprotective effects of ONO-2506 are exclusively due to its inhibition of S100B synthesis, the latter action of ONO-2506 warrants studies of the effects of this drug in the pathobiology of depression.
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PMID:Could treatment with arundic acid (ONO-2506) increase vulnerability for depression? 1679 59

S100B protein is a calcium-binding protein mostly derived from glial cells, which exerts trophic or toxic effects on neural cell depending on its concentration. It has been reported that S100B played an important role as a potential marker in psychiatric disorders. Thus, we will explore the clinical implication of S100B in major depression, especially the effect of gender and numbers of depressive episodes on S100B. The levels of serum S100B were measured with enzyme-linked immunosorbent assay (ELISA) in 54 patients with major depression and 35 age-matched healthy controls. The S100B levels in major depressed patients were significantly higher than those in controls. The serum S100B levels in female patients were significantly higher than those in male patients. Patients with recurrent depressive episodes had significantly higher S100B levels than those in first-episode depression. Serum S100B levels were significantly positive related with the numbers of depressive episode, family history and cognitive disturbance scores. These findings confirmed an increase in serum S100B levels in major depressive patients and presence of a sexual dimorphism. Moreover, numbers of depressive episodes in depression seemed to have an additional increasing effect on S100B levels.
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PMID:The effects of gender and numbers of depressive episodes on serum S100B levels in patients with major depression. 1898 42

Although the etiology of schizophrenia remains unknown, diverse neuropathological evidence suggests a disorder of synaptic connectivity. Apoptosis is a form of cell death that helps determine synaptic circuitry during neurodevelopment and altered regulation of apoptosis has been implicated in schizophrenia. Prostate apoptosis response-4 (Par-4) is an upstream regulator of apoptosis preferentially localized to synapses. Brain Par-4 levels are upregulated in response to pro-apoptotic stimuli in rodent models and in patients with classic neurodegenerative diseases. Recently, Par-4 was also found to form a complex with the dopamine D2 receptor (D2DR) in competition with the calcium-binding protein calmodulin, implicating Par-4 as an important regulatory component in normal dopamine signaling. Interestingly, mutant mice with disrupted Par-4/D2DR interaction demonstrated depressive-like behaviors, suggesting a potential role for Par-4 in both depression and schizophrenia. In this study, Par-4, D2DR and calmodulin protein levels were measured using semiquantitative Western blotting in postmortem temporal cortex in subjects with schizophrenia, major depression and bipolar disorder. Compared to normal controls, mean Par-4 levels appeared slightly lower in schizophrenia and bipolar disorder. However, in major depression, Par-4 was decreased by 67% compared to normal controls. No differences were found between any groups for calmodulin or for the D2DR 48 kDa band. The D2DR 98 kDa band was lower by 50% in the schizophrenia compared to control groups. Changes in the Par-4/D2DR signaling pathway represent a novel mechanism that may link apoptotic and dopamine signaling pathways in major depression and schizophrenia.
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PMID:Pro-apoptotic Par-4 and dopamine D2 receptor in temporal cortex in schizophrenia, bipolar disorder and major depression. 2006 57


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