UNIPROT:P08758 - FACTA Search

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Query: UNIPROT:P08758 (annexin V)
9,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

HepG2 human hepatoma cells were incubated for 24 or 48 h with various concentrations of YHK solution. After 24 h incubation, cell proliferation and cytotoxicity were determined by 3-(4,5-dimethylthiazol-2- yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2Htetrazolium (MTT) assay. Cytotoxicity or necrosis was expressed as lactate dehydrogenase (LDH) release. After exponential growth phase HepG2 cells were treated with different doses of YHK and apoptosis was assessed by using an Annexin V-FITC kit. Further, oxidative stress was measured by dichlorofluorescein-diacetate (DCFH-DA) assay. As compared to control, YHK-treated cultures showed a significant time-course decrease of the proliferation rate of HepG2 cell growth (p < 0.01). This is likely to be due to an enhanced cytotoxicity (MTT and LDH tests) (p < 0.001). On the other hand, YHK showed in vitro to significantly enhance the oxidative stress of HepG2 cell (p < 0.01) while also markedly increasing apoptosis at 72 h with cells G2/M phase arrest (p < 0.01). These data suggest that YHK seem to modulate the extrinsic and intrinsic regulators of apoptosis and sensitize tumour cells to apoptosis. These preliminary data are worth interest when considering that this nutraceutical has been shown in vitro and in vivo to exert protective anti-tumour effect by redox statusmodulating and immuno-regulatory actions. Given its lack of toxicity so far reported, such natural product might represent an effective nutritional supplement in a number of pathological conditions where a chemopreventive strategy is planned.
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PMID:In vitro study on the mechanisms of action of a novel phytotherapeutic compound against human hepatoma cells. 1751 35

Fibrates and thiazolidinediones are agonists of peroxisome proliferator-activated receptors (PPAR) alpha and gamma, pharmacologically designed to control dyslipidemia and insulin resistance, respectively. Several works have reported the toxicity of some agonists in a number of tissues. In this work we have analyzed the toxicity of two PPARalpha (WY14643 and clofibrate) and two PPARgamma (pioglitazone and ciglitazone) agonists, using three different renal proximal tubular cell lines: Opossum OK, pig LLC-PK1, and murine MCT. Cell death was determined by the activity of intracellular lactate dehydrogenase. WY14643 and ciglitazone increased cell death with LC50 values of 92-124 microM and 8.6-14.8 microM, respectively, depending on the cell line. Clofibrate and pioglitazone were, however, non-cytotoxic even at concentrations of 10 and 100 higher than the corresponding EC50, which suggests that cell death is independent of PPAR activation. Discrimination between apoptosis or necrosis was analyzed by light microscopy and stress fiber morphology, double staining with acridine orange and ethidium bromide, binding of annexin V, caspase-3 activity, and DNA laddering. With these methods, no signs of apoptosis were observed, which suggests a direct necrosis of the compounds on these renal proximal tubular cell lines.
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PMID:Cytotoxicity of peroxisome proliferator-activated receptor alpha and gamma agonists in renal proximal tubular cell lines. 1752 63

The tumor suppressor p14ARF is widely deregulated in many types of cancers and is believed to function as a failsafe mechanism, inhibiting proliferation and inducing apoptosis as cellular response to a high oncogene load. We have found that a 22-amino-acid-long peptide derived from the N-terminal part of p14ARF, denoted ARF(1-22), which has previously been shown to mimic the function of p14ARF, has cell-penetrating properties. This peptide is internalized to the same extent as the cell-penetrating peptide (CPP) TP10 and dose-dependently decreases proliferation in MCF-7 and MDA MB 231 cells. Uptake of the ARF(1-22) peptide is associated with low membrane disturbance, measured by deoxyglucose and lactate dehydrogenase (LDH) leakage, as compared to its scrambled peptide. Also, flow cytometric analysis of annexin V/propidium iodide (PI) binding and Hoechst staining of nuclei suggest that ARF(1-22) induces apoptosis, whereas scrambled or inverted peptide sequences have no effect. The ARF(1-22) peptide mainly translocates cells through endocytosis, and is found intact inside cells for at least 3 hours. To our knowledge, this is the first time a CPP having pro-apoptopic activity has been designed from a protein.
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PMID:Characterization of a novel cytotoxic cell-penetrating peptide derived from p14ARF protein. 1798 75

In view of the ability of neurotensin (NT) to increase glutamate release, the role of NT receptor mechanisms in oxygen-glucose deprivation (OGD)-induced neuronal degeneration in cortical cultures has been evaluated by measuring lactate dehydrogenase (LDH) levels, mitochondrial dehydrogenase activity with 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide levels, and microtubule-associated protein 2 (MAP2) immunoreactivity. Apoptotic nerve cell death was analyzed measuring chromatin condensation with Hoechst 33258, annexin V staining, and caspase-3 activity. Furthermore, the involvement of glutamate excitotoxicity in the neurodegeneration-enhancing actions of NT was analyzed by measurement of extracellular glutamate levels. NT enhanced the OGD-induced increase of LDH, endogenous extracellular glutamate levels, and apoptotic nerve cell death. In addition, the peptide enhanced the OGD-induced loss of mitochondrial functionality and increase of MAP2 aggregations. These effects were blocked by the neurotensin receptor 1 (NTR1) antagonist SR48692. Unexpectedly, the antagonist at 100 nM counteracted not only the NT effects but also some OGD-induced biochemical and morphological alterations. These results suggest that NTR1 receptors may participate in neurodegenerative events induced by OGD in cortical cultures, used as an in vitro model of cortical ischemia. The NTR1 receptor antagonists could provide a new tool to explore the clinical possibilities and thus to move from chemical compound to effective drug.
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PMID:Neurotensin receptor involvement in the rise of extracellular glutamate levels and apoptotic nerve cell death in primary cortical cultures after oxygen and glucose deprivation. 1806 61

Ambient oxygen (O(2)) affects the metabolism and other functions of corneal epithelial cells. The effects of O(2) concentration on the proliferation and viability of corneal epithelial cells in culture were investigated. Simian virus 40-transformed human corneal epithelial (HCE) cells were maintained at 37 degrees C in a humidified incubator containing 5% CO(2) and 95% air. The cells were subsequently transferred to a multigas incubator and exposed to 5% CO(2) and either 1, 21, or 60% O(2) plus 94, 74, or 35% N(2), respectively. Cell proliferation was evaluated by determination of cell number and measurement of the incorporation of bromodeoxyuridine. Cell lysis was quantified by measurement of the release of lactate dehydrogenase. Apoptosis was evaluated by flow cytometric analysis of cells stained with annexin V and propidium iodide as well as by immunoblot analysis of cleavage of caspase-7. The phosphorylation (activation) of Akt was also detected by immunoblot analysis. Hyperoxia (60% O(2)) inhibited the increase in cell number and the incorporation of bromodeoxyuridine apparent in HCE cells exposed to normoxia (21% O(2)). It also induced the release of lactate dehydrogenase, an increase in the proportion of apoptotic (annexin V(+), propidium iodide(-)) cells, the cleavage of caspase-7, and the phosphorylation of Akt. None of these effects was observed in cells exposed to hypoxia (1% O(2)). The amounts of the cleaved forms of caspase-3, 6, and 9 did not differ among HCE cells cultured under 1, 21, or 60% O(2). These results indicate that hyperoxia inhibited the proliferation of, and induced death by apoptosis in, cultured human corneal epithelial cells. The antiapoptotic protein Akt was also activated in cells exposed to hyperoxia, possibly reflecting a protective response to oxygen toxicity.
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PMID:Effects of ambient oxygen concentration on the proliferation and viability of cultured human corneal epithelial cells. 1818 31

Progenitor cells in the subgranular zone of the hippocampus may be of significance for functional recovery after various injuries because they have a regenerative potential to form new neuronal cells. The hippocampus has been shown to express the GH secretagogue (GHS) receptor 1a, and recent studies suggest GHS to both promote neurogenesis and have neuroprotective effects. The aim of the present study was to investigate whether GHS could stimulate cellular proliferation and exert cell protective effects in adult rat hippocampal progenitor (AHP) cells. Both hexarelin and ghrelin stimulated increased incorporation of (3)H-thymidine, indicating an increased cell proliferation. Furthermore, hexarelin, but not ghrelin, showed protection against growth factor deprivation-induced apoptosis, as measured by annexin V binding and caspase-3 activity and also against necrosis, as measured by lactate dehydrogenase release. Hexarelin activated the MAPK and the phosphatidylinositol 3-kinase/Akt pathways, whereas ghrelin activated only the MAPK pathway. AHP cells did not express the GHS receptor 1a, but binding studies could show specific binding of both hexarelin and ghrelin, suggesting effects to be mediated by an alternative GHS receptor subtype. In conclusion, our results suggest a differential effect of hexarelin and ghrelin in AHP cells. We have demonstrated stimulation of (3)H-thymidine incorporation with both hexarelin and ghrelin. Hexarelin, but not ghrelin, also showed a significant inhibition of apoptosis and necrosis. These results suggest a novel cell protective and proliferative role for GHS in the central nervous system.
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PMID:Proliferative and protective effects of growth hormone secretagogues on adult rat hippocampal progenitor cells. 1821 93

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

Although it is known that some cell types exhibit an adaptive response to low levels of cytotoxic agents, its molecular mechanism is still unclear and it has yet to be established whether this is a universal phenomenon that occurs in all cell types in response to exposure to every chemical. Hydroquinone is a synthetically produced as well as naturally occurring chemical. Human exposure to hydroquinone is predominantly through diet, cigarette smoke and occupational contact. Here, we asked whether exposure of human lung embryonic MRC-5 fibroblasts to low doses of hydroquinone leads to a cell-survival adaptive response. We further examined the possible mechanisms of an adaptive response using proteomics. We found that exposure of MRC-5 cells to low levels of hydroquinone resulted in adaptation to further exposure to lethal doses of hydroquinone at the cell-survival level, measured using the alamarBlue assay, lactate dehydrogenase leakage assay and Annexin V-FITC/PI staining. To determine the polypeptide products involved in the adaptive response, two-dimensional electrophoresis combined with mass spectrometry was performed. Twenty-three protein spots were significantly changed during the adaptive response. Among them, 21 protein spots were identified by peptide mass fingerprinting and/or peptide sequence analysis by MALDI-TOF-TOF. The identified proteins included proteins involved in energy metabolism, protein folding, redox regulation, cell structure and cell signaling. Our data suggest that the hydroquinone-induced adaptive response is a complex process involving in a modulation of diverse cellular functions, and that the redox regulation might be a common mechanism during the adaptive response.
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PMID:Induction of a cell-survival adaptive response in MRC-5 cells by hydroquinone. 1838 34

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

Application of volatile anesthetics during the onset of reperfusion reduced ischemia-induced cardiac and brain injury (anesthetic postconditioning). This study was designed to evaluate whether volatile anesthetics induced a postconditioning effect in endothelial cells. Bovine pulmonary arterial endothelial cell (BPAEC) cultures were exposed to oxygen-glucose deprivation, a condition to simulate ischemia in vitro, for 3 h. The volatile anesthetics isoflurane and desflurane were applied during the early phase of simulated reperfusion. Cell injury was quantified by lactate dehydrogenase (LDH) release and flow cytometrical measurement after annexin V and propidium iodide staining. Oxygen-glucose deprivation and the subsequent simulated reperfusion increased LDH release and annexin V-positive staining cells, a characteristic of cell apoptosis. Posttreatment with isoflurane, but not desflurane, reduced this cell injury. This protection was apparent even when 2% isoflurane was applied at 60 min after the onset of reperfusion. The isoflurane postconditioning effect was abolished by glybenclamide, a general ATP sensitive K(+) (K(ATP)) channel blocker, 5-hydroxydecanoate, a mitochondrial K(ATP) channel blocker, and chelerythrine, a protein kinase C inhibitor. Diazoxide, a mitochondrial K(ATP) channel activator, applied at the onset of reperfusion also decreased oxygen-glucose deprivation-induced endothelial cell injury. This diazoxide-induced protection was abolished by chelerythrine and 5-hydroxydecanoate. We conclude that isoflurane induced a postconditioning effect in BPAEC. The effective time window of isoflurane postconditioning was from 0 to 60 min after the onset of reperfusion. This isoflurane postconditioning effect may be mediated by mitochondrial K(ATP) channels and PKC. PKC may be downstream of mitochondrial K(ATP) channels for this isoflurane effect.
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PMID:Isoflurane induces a postconditioning effect on bovine pulmonary arterial endothelial cells exposed to oxygen-glucose deprivation. 1946 84

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