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)

We have previously proposed that cytokine-stimulated nitric oxide (NO) production is responsible for reversible myocardial depression in sepsis, trauma and ischemia. NO previously has been found to inhibit mitochondrial activity in other cell types. Accordingly, we sought to determine if cytokine-stimulated NO production inhibited cardiac myocyte mitochondrial activity. Treatment of neonatal rat cardiac myocytes with interleukin-beta (IL-1) resulted in the expression of mRNA for inducible NO synthase (iNOS) and stained positively for iNOS protein by immunohistochemistry. No iNOS staining was detected in untreated cells. IL-1 treatment resulted in significant nitrite levels vs control over 48 hrs (4.2 +/- 0.7 vs 0.3 +/- 0.2 nmol/1.25 x 10(5) cells, respectively) (n = 12) that was inhibited by 1mM NMA (0.3 +/- 0.2 nmoles; p < .01; n = 12). Mitochondrial activity was assessed by the MTT colorimetric assay using (3-4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and OD 570-630. Mitochondrial activity was significantly inhibited by IL-1 vs control cells (0.436 +/- 0.01 vs 0.608 +/- 0.03) and reversed by 1mM NMA (0.549 +/- 0.03) or removal of IL-1 (0.662 +/- 0.02) (p < .01; n = 12 for each). These data strongly suggest that cytokine-stimulated NO production by cardiac myocytes results in reversible inhibition of mitochondrial activity.
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PMID:Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. 765 17

The thymoma cell line EL4.IL-2 (EL-4) was used as a T-cell model to assess the immunotoxic effects of several mycotoxins produced by the Aspergillus-Penicillium and the Fusarium groups. EL-4 cells were stimulated with phorbol 12-myristate 12-acetate (PMA) in the presence of mycotoxins at various concentrations for 5 d and culture supernatants were analyzed for interleukins (IL) IL-2 and IL-5 by enzyme-linked immunosorbent assay (ELISA). The cytokine effects were further related to proliferation and cell viability using the MTT [3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide] assay with absorbance at 570 nm (A570) as the endpoint indicator. IL-2 and IL-5 levels were dramatically increased by cyclopiazonic acid at 50-1000 ng/ml, whereas IL-2 was significantly decreased at 10 microgram/ml. Proliferation was slightly increased at 100-1000 ng/ml cyclopiazonic acid but markedly depressed at 5 and 10 microgram/ml. When EL-4 cells were exposed to 5 and 10 microgram/ml of ochratoxin A, IL-2 production was markedly increased while IL-5 production was significantly decreased. The A570 was significantly decreased by ochratoxin A at 10 microgram/ml. IL-2 and Il-5 production was almost totally suppressed by patulin at concentrations > or = 500 ng/ml and by T-2 toxin at > or = 5 ng/ml. These effects occurred concurrently with marked depression of A570 in the MTT assay. Although A570 was unaffected by either zearalenone or alpha-zearalenol exposure, both IL-2 and IL-5 levels were significantly elevated by these toxins at 5 or 10 microgram/ml. IL-2 and IL-5 production were not affected in EL-4 cells cultured with either the Aspergillus-Penicillium toxins aflatoxin B1 and secalonic acid or the Fusarium toxins wortmannin, fumonisin B1, or fusaric acid at concentrations up to 10 microgram/ml. In total, the EL-4 culture studies indicated that cyclopiazonic acid, ochratoxin A, zearalenone, and alpha-zearalenol could stimulate cytokine production whereas patulin and T-2 toxin were inhibitory. Cytokine dysregulation was not always related directly to perturbations in proliferation. The results suggest that the EL-4 thymoma cell line could be a simple and effective in vitro model for evaluating immunotoxicity of various classes of environmental chemicals.
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PMID:Effects of mycotoxins on cytokine production and proliferation in EL-4 thymoma cells. 869 8

Following nephrotoxic injury, renal repair is dependent on tubular regeneration. In the case of myoglobinuric acute renal failure (ARF), persistence of myoglobin within tubular cells, or sublethal injury sustained at the height of exposure to it, might retard this process. To test this hypothesis, a human proximal tubular cell line (HK-2) was cultured for 24 hours in the absence or presence of clinically relevant myoglobin concentrations (0.5, 1, 2, 4 mg/ml). Immediately following myoglobin removal, lethal cell injury (vital dye uptake), lipid peroxidation, and DNA damage (alkaline unwinding assay) were assessed. The extent of cell proliferation was estimated over the next four days by a tetrazolium based (MTT) assay and by determining total intracellular LDH. Myoglobin's effects on protein and DNA synthesis were also assessed (35S-methionine and bromodeoxyuridine incorporation, respectively). Myoglobin induced dose-dependent lipid peroxidation (malondialdehyde generation) and cell death (up to 80% vital dye uptake with the 4 mg/ml challenge). Although 1 mg/ml myoglobin caused no cell death, it induced nearly complete growth arrest. This lasted for approximately three days following myoglobin removal from the media. Neither of two control proteins (albumin; lysozyme) nor a second nephrotoxin (gentamicin; 1 mg/ml) reproduced this effect. The 1 mg/ml myoglobin challenge caused an 80 to 90% depression in protein and DNA synthesis. It also induced significant DNA damage, as assessed by the alkaline unwinding assay (P < 0.01). Iron chelation therapy (deferoxamine) mitigated myoglobin-induced cell killing. However, its addition following myoglobin loading worsened HK-2 outgrowth by exerting a direct anti-proliferative effect. These results indicate that: (1) sublethal myoglobin toxicity can induce transient proximal tubular cell growth arrest, potentially slowing recovery from ARF; (2) this effect correlates with, and could result from, heme-induced DNA damage and a blockade in DNA/protein synthesis; and (3) deferoxamine can inhibit proximal tubular cell proliferation. This possibility needs to be considered in designing clinical trials with DFO for myohemoglobinuric ARF.
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PMID:Myoglobin inhibits proliferation of cultured human proximal tubular (HK-2) cells. 887 53

To study the cytophysiological effects of ethanol systematically, L929 cells, a fibroblastic cell line derived from mouse connective tissue, were exposed to various concentrations of ethanol (12.5, 50, 100 and 200 mM) for short (3 and 6 h) and longer (24 or 26 h) durations. Ethanol-induced cellular responses were analysed by a combination of the following assays: number of cells, amounts of DNA and protein, MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay and cell cycle. Ethanol dose-dependently suppressed these cellular functions, except that 12.5 mM exposures for both 6 and 26 h increased the amount of protein in spite of almost no change in other cellular functions, compared to the control. The most marked dose-dependency was observed in a reduction of formazan product in an MTT assay after both 6 and 26 h exposures to ethanol, being independent of the number of cells and probably reflecting dose-dependent depression of mitochondrial respiration. A G2 + M block in the cell cycle, an inhibition of cell division, was induced after short-term exposures (3 and 6 h) to 100 and 200 mM ethanol, but the block was released before 24 h had passed. Alternatively, prolonged exposures (24 h) to 50-200 mM ethanol induced a G0/G1 block, resulting in a decrease in the amount of DNA below the control value. Moreover, the percentage of the S phase was decreased gradually and dose-dependently throughout the 24 h exposure. Thus, high concentrations of ethanol (50, 100 and 200 mM) perturbed the cell cycle progression by causing both a transient G2 + M block (an inhibition of mitosis) and a continuous G0/G1 block, though the latter was masked by the G2 + M block during short-term exposure. The cells seem finally to acquire some tolerance to ethanol so as to pass through mitosis, but much less tolerance to pass through the checkpoint from the G1 to the S phase, which results in a decline in proliferation.
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PMID:Ethanol induces transient arrest of cell division (G2 + M block) followed by G0/G1 block: dose effects of short- and longer-term ethanol exposure on cell cycle and cell functions. 910 8

Peritonitis remains a major problem in peritoneal dialysis. The incidence of peritonitis may be reduced by the use of more "biocompatible" peritoneal dialysis solutions that do not impair local host defense mechanisms, such as occurs with conventional lactate-buffered glucose solutions. In the present study, we investigated the use of bicarbonate and lactate as buffer systems and glucose, amino acids, and glucose polymer as osmotic agents on specific cellular functions of isolated fresh blood monocytes in vitro. The bicarbonate-buffered solutions had a physiologic pH (7.0 to 7.6). Lactate-buffered solutions were tested with a pH between 5.5 and 7.3. RPMI 1640 (Roswell Park Memorial Institute, supplied by Biochrom, Berlin, Germany) and phosphate-buffered saline were used as control mediums. The test solutions were incubated with 200,000 monocytes/mL for 45 minutes followed by a 1:1 mix with RPMI 1640 (with supplements) during a 24- or 4-hour tetrazolium bromide test (MTT test) recovery period. Constitutive and lipopolysaccharide (LPS)-stimulated release of interleukin-1beta (IL-1beta) and IL-6 in the supernatants as parameters of cellular host defense and lactate dehydrogenase concentrations and MTT-formazan production as parameters for cell cytotoxicity were measured. Significantly higher IL-6 and IL-1beta release was found in the bicarbonate-buffered solutions, both under basal conditions and after LPS stimulation, compared with the lactate-buffered solutions (LPS stimulation: 1% amino acids/34 mmol/L bicarbonate, IL-1beta: 1,166 +/- 192 pg/mL; 1.5% glucose/34 mmol/L bicarbonate, IL-1beta: 752 +/- 107 pg/mL; 1.5% glucose/35 mmol/L lactate/pH 5.5, IL-1beta: 174 +/- 51 pg/mL). Some of these differences could even be detected in spent dialysate after a 6-hour dwell in continuous ambulatory peritoneal dialysis patients (n = 10). A lower degree of cellular cytotoxicity (lactate dehydrogenase activity) and better-preserved metabolic activity (MTT test) also were found for the bicarbonate-buffered solutions. Amino acids (1%) proved to be comparable to glucose (1.5%) as an osmotic agent at a neutral pH with regard to LPS-stimulated cytokine release and cytotoxicity. The incubation with a glucose polymer solution (7.5% glucose polymer in phosphate-buffered saline, pH 7.3) resulted in a significantly lowered cytokine release (LPS stimulation: IL-1beta, 69 +/- 19 pg/mL) compared with the other solutions with neutral pH (P < 0.01). These results suggest that bicarbonate as a buffer provided better biocompatibility with regard to mononuclear cytokine release and viability compared with lactate. Amino acids and glucose were equivalent to these parameters at a physiologic pH. The glucose polymer solution, however, was associated with a marked depression of cytokine release.
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PMID:Osmotic agents and buffers in peritoneal dialysis solution: monocyte cytokine release and in vitro cytotoxicity. 929 71

Neurotoxicity of beta42 (20 microM) in cultured rat hippocampal neurons was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release methods as quantitative assays of cell death, and both methods indicated that propentofylline (PPF) had the ability to protect the neurons against the toxicity, although these two assay methods revealed different mechanisms for the toxic effect of beta42. Promotion of the active exocytotic system of the cells was suggested after treatment with beta42 in the MTT assay and in determination of 9-aminoacridine (AA) excretion from the preloaded cells after 24-h treatment with beta42. The promotion of AA exocytosis was blocked by the addition of PPF (20 microg/ml). The preventive effect of PPF on the neurotoxicity of beta42 has been proposed to be caused by elevation of the intracellular level of cAMP as a result of depression of the hydrolytic activity of cells.
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PMID:Evaluation of neurotoxicity of alzheimer's amyloid beta protein (beta42) in cultured hippocampal cells and its prevention by propentofylline. 1087 49

Cerebral inflammation plays a role in diseases such as multiple sclerosis (MS), Alzheimer's disease (AD), and depression. Iron is involved in infection and inflammation through free radical production. Theoretically transferrin should prohibit iron from participating in oxidative reactions, but transferrin has also been found to promote free radical damage. We reported previously that isolation of transferrin from plasma by ion exchange column chromatography produced a broad pink protein band that subsequently separated on a gel filtration column into three proteins containing many metals. In this study some properties of the three proteins were studied in 20 volunteers. Protein 3 (identified as transferrin by nephelometry) contained the most iron while Protein 1 (called "toxiferrin") contained significantly less iron (p < 0.00001). Plasma from volunteers obtained under conditions of infection/inflammation with fever (n = 5) had a significantly increased toxiferrin to transferrin ratio compared to healthy volunteers (n = 15; p < 0.001). In vitro, Protein 2 and transferrin inhibited lipid peroxidation, while toxiferrin (possibly a protease degradation product of transferrin), enhanced lipid peroxidation. Also, toxiferrin (1 mg/mL) caused a significant increase in viability of monocytes as measured by the 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyl tetrazolium bromide (MTT) reduction test, as well as the morphological transformation of monocytes to macrophages.
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PMID:Biochemical model for inflammation of the brain: the effect of iron and transferrin on monocytes and lipid peroxidation. 1521 10

The standard extracts of Hypericum perforatum L. (SEHP), a well-known medicinal plant, are used for the treatment of depression, exhibited upgrading and significant protective effects on the trauma of PC12 cells induced by 200 microM H2O2 in a dose-dependent manner within 24-hour treatment. Cell viability was assessed by the MTT method, and in situ cellular hydrogen peroxide (H2O2)-induced oxidative stress was examined by measurement of reactive oxygen species (ROS) formation using CDCFH procedures. Intra- and extra-cellular ROS levels decreased significantly to 71.9% and 50.0% of the control at a moderate concentration of 20 microg/ml, respectively, suggesting that SEHP could easily enter the cells and play important roles in reducing ROS levels. Our results were proved by detection of DNA fragmentation and inspection of cell morphology of PC12 cells. SEHP can obviously block DNA fragmentation and prevent the cells from shrinking and turning round of H2O2-induced apoptosis in PC12 cells at concentrations of 10 approximately 100 microg/ml. This data suggests SEHP may be a candidate for application in neurodegenerative diseases such as Alzheimer's disease or Parkinson's disease.
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PMID:Neuroprotective effects of Hypericum perforatum on trauma induced by hydrogen peroxide in PC12 cells. 1534 23

To explore the effect of glycosyl-phosphatidyl inositol-specific phospholipase D (GPI-PLD) on the adhesion function of bone marrow mononuclear cell from patients with myeloid leukemia and analyze its mechanism, the activity of GPI-PLD in bone marrow mononuclear cell from the patients were measured by using GPI-anchored placental alkaline phosphatase (PLAP) as substrate and Triton-X114 partitioning; the adhesion rate and CD24 expression of these cells were measured by MTT and immunohistochemical method respectively, when these cells were or were not treated by 1 mmol/L 1,10-phenanthroline for 5 hours. The results showed that the GPI-PLD activity of bone marrow mononuclear cells from the patients was significantly inhibited after being treated by 1 mmol/L 1, 10-phenanthroline for 5 hours [(42.08 +/- 7.21)% vs (5.4 +/- 2.96)%], while the adhesion rate and the expression of CD24 of these cells were increased [(49.78 +/- 26.73)% vs (61.19 +/- 29.14)%, (16.02 +/- 9.68)% vs (18.5 +/- 11.14)%, respectively)]. It is concluded that depression of GPI-PLD activity can increase the adhesion rate of bone marrow mononuclear cells from the patients while the CD24 expression is enhanced.
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PMID:[Effect of GPI-PLD on adhesion function of bone marrow mononuclear cell from patients with myeloid leukemia and its mechanism]. 1597 22

Fluoxetine is a widely used antidepressant compound which inhibits the reuptake of serotonin in the central nervous system. Recent studies have shown that fluoxetine can promote neurogenesis and improve the survival rate of neurons. However, whether fluoxetine modulates the proliferation or neuroprotection effects of neural stem cells (NSCs) needs to be elucidated. In this study, we demonstrated that 20 microM fluoxetine can increase the cell proliferation of NSCs derived from the hippocampus of adult rats by MTT test. The up-regulated expression of Bcl-2, Bcl-xL and the cellular FLICE-inhibitory protein (c-FLIP) in fluoxetine-treated NSCs was detected by real-time RT-PCR. Our results further showed that fluoxetine protects the lipopolysaccharide-induced apoptosis in NSCs, in part, by activating the expression of c-FLIP. Moreover, c-FLIP induction by fluoxetine requires the activation of the c-FLIP promoter region spanning nucleotides -414 to -133, including CREB and SP1 sites. This effect appeared to involve the phosphatidylinositol-3-kinase-dependent pathway. Furthermore, fluoxetine treatment significantly inhibited the induction of proinflammatory factor IL-1beta, IL-6, and TNF-alpha in the culture medium of LPS-treated NSCs (p<0.01). The results of high performance liquid chromatography coupled to electrochemical detection further confirmed that fluoxentine increased the functional production of serotonin in NSCs. Together, these data demonstrate the specific activation of c-FLIP by fluoxetine and indicate the novel role of fluoxetine for neuroprotection in the treatment of depression.
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PMID:Fluoxetine up-regulates expression of cellular FLICE-inhibitory protein and inhibits LPS-induced apoptosis in hippocampus-derived neural stem cell. 1654 75


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