Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P08758 (annexin V)
 9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alzheimer's disease (AD) is a common neurodegenerative disorder, but the initiating molecular processes contributing to neuronal death are not well understood. AD is associated with elevated soluble and aggregated forms of amyloid beta (Abeta) and with oxidative stress. Furthermore, there is increasing evidence for a detrimental role of iron in the pathogenic process. In this context, iron chelation by compounds such as 3-hydroxypyridin-4-one, deferiprone (Ferriprox) may have potential neuroprotective effects. We have evaluated the possible neuroprotective actions of deferiprone against a range of AD-relevant insults including ferric iron, H(2)O(2) and Abeta in primary mouse cortical neurones. We have investigated the possible neuroprotective actions of deferiprone (1, 3, 10, 30 or 100 microM) in primary neuronal cultures following exposure to ferric iron [ferric nitrilotriacetate (FeNTA); 3 and 10 microM], H(2)O(2) (100 microM) or Abeta1-40 (3, 10 and 20 microM). Cultures were treated with deferiprone or vehicle either immediately or up to 6 h after the insult in a 24-well plate format. In order to elucidate a possible neuroprotective action of deferiprone against Parkinson's disease relevant insults another group of experiments were performed in the human neuroblastoma catecholaminergic SHSY-5Y cell line. SHSY-5Y cells were treated with MPP(+) iodide, the active metabolite of the dopaminergic neurotoxin MPTP and the neuroprotective actions of deferiprone evaluated. Cytotoxicity was assessed at 24 h by lactate dehydrogenase release, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium-bromide turnover (FeNTA and hydrogen peroxide) and morphometric analysis of cell viability by Hoechst 33324/propidium iodide (FeNTA, Abeta and MPP(+)) or 6-carboxyfluorescein diacetate and annexin V-Cy3 (Abeta). The present study demonstrates that deferiprone protects against FeNTA, hydrogen peroxide, MPP(+) and Abeta1-40-induced neuronal cell death in vitro, which is consistent with previous in vitro and in vivo studies that have demonstrated similar protection with other iron chelators.
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PMID:Neuroprotective actions of deferiprone in cultured cortical neurones and SHSY-5Y cells. 1833 85

The methanolic and methane dichloride extracts of aerial parts of Larrea divaricata Cay. (Jarilla) plants exhibited a pronounced cytotoxic effect by arresting cell viability at a level of 35% against the MCF-7 cell line, a human breast adenocarcinoma, while only a weak cytotoxic effect was observed for the aqueous extract. Apoptosis was detected by flow cytometry, using annexin V and by cytological detection with fluorescein diacetate / propidium iodide staining. The annexin V, as well as the uptake of fluorescein diacetate/propidium iodide staining, revealed that methanolic and methane dichloride extracts of L. divaricata treatment of cells resulted in a rapid plasma membrane perturbation and triggered cellular death (>70%). Methanolic extracts were submitted to further treatment by bioassay-guided purification, involving fractionation and chromatography. 0.1% (w/w) nordihydroguaiaretic acid (NDGA) was found, which displayed weak citotoxic activity.
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PMID:Organic extracts of Larrea divaricata Cav. induced apoptosis on tumoral MCF7 cells with an higher cytotoxicity than nordihydroguaiaretic acid or paclitaxel. 1847 37

The hypoglycemia and serum limitation-induced cell death in cultured PC12 cells represents a useful in vitro model for the study of brain ischemia and neurodegenerative disorders. Salidroside is a phenylpropanoid glycoside isolated from Rhodiola rosea L., a traditional Chinese medicinal plant, and has displayed a broad spectrum of pharmacological properties. In this study, MTT assay, Hoechst 33342 staining, and flow cytometry with annexin V/PI staining collectively showed that pretreatment with salidroside attenuated, in a dose-dependent manner, cell viability loss, and apoptotic cell death in cultured PC12 cells induced by hypoglycemia and serum limitation. RT-PCR, Western blot analysis, and enzymatic colorimetric assay indicated the changes in expression levels of Bcl-2, Bax, and caspase3 in PC12 cells on exposure to hypoglycemia and serum limitation with and without salidroside pretreatment, respectively. Rhodamine 123 staining and flow cytometry with 2',7'-Dichlorofluorescin diacetate staining revealed the changes in the mitochondrial membrane potential and radical oxygen species (ROS) production in PC12 cells on exposure to hypoglycemia and serum limitation with and without salidroside pretreatment, respectively. The experimental results suggest that salidroside protects the PC12 cells against hypoglycemia and serum limitation-induced cytotoxicity possibly by the way of the modulation of apoptosis-related gene expression, the restoration of the mitochondrial membrane potential, and the inhibition of the intracellular ROS production. Our findings might raise a possibility of potential therapeutic applications of salidroside for preventing and treating cerebral ischemic and neurodegenerative diseases.
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PMID:Neuroprotective effects of salidroside in the PC12 cell model exposed to hypoglycemia and serum limitation. 1848 Nov 68

Previous investigations have revealed that dental monomers could affect intracellular pathways leading to cell survival or cell death. Mitogen-activated protein kinase (MAPK) and protein kinase B (AKT) might mediate cell responses as well as cell survival and apoptosis. The purpose of this study was to evaluate the effects of 2-hydroxyethyl methacrylate (HEMA) on the ERK1/2 and AKT pathways in human primary pulp fibroblasts (HPCs). HPCs were treated with various concentrations of HEMA, after which viability and reactive oxygen species levels were determined by flow cytometry with Annexin V-PI staining and 2,7-dichlorofluorescine diacetate, respectively. Whole-cell extracts were immunoblotted with anti-P-Akt or anti-P-ERK1/2. Cell viability decreased in a dose-dependent manner after HEMA exposure, showing a significant decrease with 10 mmol/L HEMA (p < .05). HEMA treatment resulted in a 4-fold increase in reactive oxygen species formation (p < .05). A short HEMA exposure (30-90 minutes) increased ERK1/2 phosphorylation, whereas a decrease in the AKT phosphorylation was observed. Selective inhibitors of the ERK (PD98059) and AKT (LY294002) pathways amplified HPC cell damage after HEMA exposure. Our findings demonstrated that HEMA exposure modulates the ERK and AKT pathways in different manners, and that in turn, they function in parallel to mediate pro-survival signaling in pulp cells subjected to HEMA cytotoxicity.
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PMID:Effect of 2-hydroxyethyl methacrylate on human pulp cell survival pathways ERK and AKT. 1849 89

In the course of searching for novel cytotoxic compounds which can be used in chemotherapy, several Traditional Chinese Medicines (TCM) have been screened by bioassay-guided fractionation and isolation. An extract of rhizomes of Iris tectorum Maxim., a TCM used to treat cancer, exhibited highest potency and led to the isolation of two flavonoids, 7-O-methylaromadendrin and tectorigenin, and four iridal-type triterpenes, iritectols A and B, isoiridogermanal and iridobelamal A. The cytotoxicities of the isolated compounds against four human cancer cell lines were evaluated by the SRB assay. Iritectol B, isoiridogermanal and iridobelamal A showed similar cytotoxicity with IG(50) around 11 microM and 23 microM against MCF-7 and C32 cell lines, respectively. Cell cycle-specific inhibition and apoptosis induced by the isolated compounds were determined using flow cytometry with two sets of co-labelling systems: annexin V-FITC/propidium iodide and fluorescein diacetate/propidium iodide. Iritectol B demonstrated dose-dependent apoptotic effect against COR-L23 cells with an apoptotic rate of 33% at 100 microM. Tectorigenin (an analogue of genistein) showed cell cycle specific inhibition and arrested cells at G(2)/M phase up to 400 microM, but did not demonstrate apoptotic effect against COR-L23 cells up to 1 mM. The overall activities of isolated compounds observed in the present study support the traditional use of Iris tectorum Maxim. in the treatment of cancer.
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PMID:Cytotoxic effects of compounds from Iris tectorum on human cancer cell lines. 1850 14

Neutrophil apoptosis is critical for final resolution of the inflammation in the tissues and for maintenance of neutrophil homeostasis under normal condition. An early hallmark of apoptotic cells is translocation of phosphatidylserine (PS) residues, normally located in the inner leaflet of cellular membrane, to the external cell surface; exposed PS is recognized by specific PS receptors on disposing cells. Here we report an improved procedure to detect neutrophil apoptosis by simultaneous staining for exposed PS with Cy3-labeled annexin V (Cy3) and for membrane integrity with the vital dye 6-carboxyfluorescein diacetate (6-CFDA) based on the APOAC apoptosis detection kit (Sigma). Spontaneous apoptosis was evaluated in ovine neutrophils cultured ex vivo for 18 h. We investigated the multiple parameters involved in the assay, i.e. the type of fixative (methanol, paraformaldehyde, or no fixation) and the type of slide (coated with Vectabond, polylysine or Parafilm((R))). Results indicated that both the adhesion to the slide and the fixation can modify neutrophil functional status and morphology, which result in misleading apoptosis detection. In order to minimize these artifacts, we have developed an improved APOAC assay procedure, staining cells while in suspension and using Parafilm((R)) coated slides.
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PMID:Improved apoptosis detection in ovine neutrophils by annexin V and carboxyfluorescein diacetate staining. 1900 7

Quinones have diverse pharmacological properties including antibacterial, antifungal, antiviral, anti-inflammatory, antipyretic and anticancer activity. The cytotoxic potential of 1,4-naphthoquinone (NQ14) was studied against B16F1 melanoma cells grown in vitro. NQ14 treatment resulted in a concentration-dependent cytotoxicity as indicated by MTT assay and lactate dehydrogenase leakage assay. Depletion in cellular glutathione levels after 1h incubation with NQ14 correlated with the corresponding increase in reactive oxygen species generation as determined by 2',7'-dicholorofluorescein diacetate assay suggests the role of oxidative stress in cell death. The frequency of micronucleated binucleate cells increased with increasing doses of NQ14 with a corresponding decrease in the cytokinesis block proliferation index indicating the drug induced genotoxicity and cell division delay. Further, a dose-dependent decrease in the clonogenic cell survival indicated the potential of NQ14 to inhibit cell proliferation contributing to cell death. The cell death after NQ14 treatment may be attributed to apoptosis as seen in DNA ladder pattern along with necrosis as indicated in flow cytometric analysis of Annexin V/PI stained cells. Results of the present study demonstrate the cytotoxic and genotoxic potential of NQ14 by the induction of oxidative stress mediated mechanisms leading to tumor cell kill.
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PMID:Cytotoxic, genotoxic and oxidative stress induced by 1,4-naphthoquinone in B16F1 melanoma tumor cells. 1912 82

In Arunachal Pradesh and other sub-Himalayan areas of India, accidental consumption of Senecio plants by yaks is often fatal as the plant contains toxic alkaloids like Seneciophylline. The present investigation was undertaken to demonstrate the pro-oxidant effects of an ethanolic extract of Senecio chrysanthemoides (S-EtOH). S-EtOH impaired viability in macrophages, the IC(50) being 13.8+/-1.11 microg/mL. The effect of S-EtOH (1 microg/mL) on generation of reactive oxygen species (ROS) in macrophages was measured by flow cytometry using 2',7'-dichlorofluorescein diacetate (H(2)DCFDA) where it caused a significant increase in the mean fluorescence channel (MFC) from 8.55+/-0.03 to 47.32+/-2.25 (p<0.001). S-EtOH also effected a 3.8-fold increase in extracellular nitric oxide (NO) generation from 4.90+/-0.72 microM to 18.79+/-0.32 microM (p<0.001), a 2.2-fold increase in intracellular NO production, the MFC increasing from 14.95+/-0.48 to 33.34+/-1.66 (p<0.001), and concomitantly depleted non protein thiols as analyzed by flow cytometry using mercury orange, with a reduction in MFC from 632.5+/-49.44 to 407.4+/-12.61 (p<0.01). Additionally, S-EtOH (14 microg/mL, 24h) caused apoptosis as evident by increased Annexin V binding and terminal deoxynucleotidyl transferase mediated dUTP DNA nick end labeling. Taken together, the cytotoxicity of S-EtOH can be partly attributed to its capacity to inflict oxidative damage via generation of both reactive oxygen and nitrogen species culminating in apoptosis.
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PMID:Cytotoxicity of Senecio in macrophages is mediated via its induction of oxidative stress. 1919 69

Thymoglobulin is an antithymocyte globulin preparation used in hematopoietic stem cell transplantation (HSCT) to prevent rejection and graft-versus-host disease. Because natural killer (NK)-cell alloreactivity improves HSCT outcome, but only in patients receiving thymoglobulin, we investigated the in vitro effects of thymoglobulin on purified NK cells. Thymoglobulin binding to NK cells and NK-cell activation were assessed by flow cytometry. NK surface targets for thymoglobulin were determined by competition inhibition assays using monoclonal antibodies. Chromium 51 (Cr) release assay, Annexin V combined with 7-amino-actinomycin D staining, and carboxyfluorescein diacetate succinimidyl ester staining were used to study cytotoxic activity, apoptosis/cell death, and NK-cell proliferation, respectively. Interferon (IFN)-gamma production was determined by ELISA. Thymoglobulin, thymoglobulin derived-F(ab')2 fragments as well as rabbit IgG bound NK cells, and competed strongly with anti-CD16. Thymoglobulin enhanced the expression of activation (CD69 and NKG2D) and degranulation (CD107a) markers on NK cells. It competed with CD18 binding and decreased NK activity, but not interleukin-15-induced killer activity. Effects on apoptosis/cell death and proliferation were minimal. F(ab')2 fragments and rabbit IgG strongly induced IFN-gamma production by NK cells. Thymoglobulin binds to NK cells by CD16 by its variable and constant regions. The decrease in NK-cell cytotoxic activity is restored by interleukin-15, and contrasts sharply with the induction of activation, degranulation, and IFN-gamma production. These data support the hypothesis that thymoglobulin treatment is required to observe the improvement in HSCT outcome by NK-cell alloreactivity.
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PMID:Binding of thymoglobulin to natural killer cells leads to cell activation and interferon-gamma production. 1930 82

Carthamus tinctorius L. (safflower) is one of the most commonly used Chinese herbal medicines to prevent and treat cardiac disease in clinical practice. However, the mechanisms responsible for such protective effects remain largely unknown. In this study, we investigated the anti-myocardial ischemia effects of a purified extract of C. tinctorius (ECT) both in vivo and in vitro. An animal model of myocardial ischemia injury was induced by left anterior descending coronary artery occlusion in adult rats. Pretreatment with ECT (100, 200, 400, 600 mg/kg body wt.) could protect the heart from ischemia injury by limiting infarct size and improving cardiac function. In the in vitro experiment, neonatal rat ventricular myocytes were incubated to test the direct cytoprotective effect of ECT against H(2)O(2) exposure. Pretreatment with 100-400 microg/ml ECT prior to H(2)O(2) exposure significantly increased cell viability as revealed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. ECT also markedly attenuated H(2)O(2)-induced cardiomyocyte apoptosis, as detected by Annexin V and PI double labeling with flow cytometry. The intracellular level of reactive oxygen species (ROS) was shown by 2',7'-dichlorofluorescin diacetate (DCFH-DA), and ECT pretreatment significantly inhibited H(2)O(2)-induced ROS increase. We made a preliminary examination of the signaling cascade involved in ECT mediated anti-apoptotic effects. Phosphatidylinositol 3 kinase (PI3K) inhibitor (LY294002) blocked the cytoprotective effect conferred by ECT. Taken together, our findings provide the first evidence that the cardioprotective effects of ECT in myocardial ischemia operate partially through reducing oxidative stress induced damage and apoptosis. The protection is achieved by scavenging of ROS and mediating the PI3K signaling pathway.
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PMID:Protective effects of purified safflower extract on myocardial ischemia in vivo and in vitro. 1939 8


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