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)

Induction of apoptosis represents a potential reaction of endothelial cells (ECs) after injury of the vascular endothelium. Beneficial effects of n-3 polyunsaturated fatty acids (PUFAs) in vascular diseases are widely recognized although the responsible mechanisms are not fully understood. Because it is not known whether PUFAs modulate EC apoptosis, we investigated the effects of n-3 and n-6 PUFAs on 4-hydroxynonenal (HNE)-induced EC apoptosis by annexin V staining and caspase-3 activation assays. Pretreatment with the n-3 fatty acid docosahexaenoic acid (DHA) reduced HNE-induced EC apoptosis. DHA-treated cells did not show the pronounced drop in intracellular GSH after HNE exposure seen in vehicle- or n-6 arachidonic acid-treated cells. This is most likely due to increased GSH levels in DHA-treated cells. Furthermore, DHA pretreatment increased ciap1 mRNA levels and transfection of cIAP1 small interfering RNA abolished the protective effect of DHA in HNE-induced apoptosis in HUVECs. Thus pretreatment of HUVECs with DHA reduces HNE-induced oxidative stress and apoptosis, and the protective effects of DHA seem to be dependent on cIAP1. The results provide a possible new mechanism for the atheroprotective effects of n-3 fatty acids in vascular disease.
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PMID:Docosahexaenoic acid induces ciap1 mRNA and protects human endothelial cells from stress-induced apoptosis. 1647 61

Cadmium (Cd) is a well-known environmental carcinogen and a potent immunotoxicant. It induces thymocyte apoptosis in vitro. However, the mode of action is unclear. In this study, we examined the effect of Cd (10, 25 and 50microM) on mitochondrial membrane potential and caspase-3 as well as oxidative stress markers in murine thymocytes. The cadmium induced apoptosis occurred in a concentration and time dependent manner. The early markers of apoptosis-loss in mitochondrial membrane potential and caspase-3 activation were evident as early as 1.5h by 50microM Cd. Enhanced reactive oxygen species (ROS) generation and glutathione (GSH) depletion were observed at 60min, prior to the lowering of mitochondrial membrane potential. The Cd induced DNA damage as depicted by internucleosomal fragmentation on agarose and histone associated mono- and oligonucleosomes detection by ELISA, corrobated with the apoptotic DNA (sub-G(1) population) and total apoptotic cells by Annexin V binding assay. The number of cells in sub-G(1) population increased to 66% at 50microM Cd concentration and the distribution of early and late apoptotic cells was 47% and 15%, respectively. Addition of N-acetylcysteine and pyrrolidine dithiocarbamate (thiol antioxidants) to the Cd treated cells, lowered the sub-G(1) population, inhibited the ROS generation and raised the GSH levels. Buthionine sulfoximine (GSH depletor) on the other hand, enhanced both the ROS production and the sub-G(1) fraction. These results clearly demonstrate the apoptogenic potential of Cd in murine thymocytes, following mitochondrial membrane depolarization, caspase activation and ROS and GSH acting as critical mediators.
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PMID:Influence of cadmium on murine thymocytes: potentiation of apoptosis and oxidative stress. 1656 67

Sevoflurane is an inhalation anesthetic used for general anesthesia. Several studies have demonstrated that reactive oxygen species (ROS) exist in cardioprotection when preconditioned with sevoflurane. Moreover, sevoflurane can also directly trigger the formation of peroxynitrite. Up to now, information pertinent to the effect of sevoflurane on cellular injuries in human polymorphonuclear neutrophils (PMN) is scant. In this study, we demonstrated that sevoflurane significantly increases intracellular H2O2 and/or peroxide, superoxide, and nitric oxide (NO) in PMN within 1h treatment. Intensification of intracellular glutathione (GSH) depletion in PMN has been demonstrated with the presence of sevoflurane. Inhibition of sevoflurane-mediated intracellular H2O2 and/or peroxide in PMN by catalase, mannitol, dexamethasone, N-acetylcysteine (NAC) and trolox, but not superoxide dismutase (SOD) pretreatment, was observed. Among them, catalase has the best effect scavenging intracellular H2O2 and/or peroxide, suggesting that H2O2 is the major ROS during sevoflurane treatment. Two apoptotic critical factors-lowering of the mitochondrial transmembrane potential (DeltaPsim) and activation of caspase 3/7-were significantly increased after 1h of sevoflurane treatment. Apoptosis of PMN were determined by comet assay and flow cytometric analysis of annexin V-FITV protein binding to the cell surface. Exposure of PMN to sevoflurane markedly increased apoptosis in a dose-dependent manner. In summary, these results are important for demonstrating the oxidative stress and cellular injury on sevoflurane-treated human PMN.
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PMID:Sevoflurane-induced oxidative stress and cellular injury in human peripheral polymorphonuclear neutrophils. 1667 24

beta-Amyloid causes apoptosis and death in cultured neurons that may be mediated by generation of reactive oxygen species. Since ascorbic acid concentrations are relatively high in brain, we tested whether and how this antioxidant might protect cultured SH-SY5Y neuroblastoma cells from apoptotic cell death. SH-SY5Y cells did not contain ascorbate in culture but readily took it up to achieve intracellular concentrations several-fold those of GSH. Treatment of cells with 2-10 microM beta-amyloid(25-35) decreased both intracellular ascorbate and GSH without affecting rates of ascorbate transport, which suggests that the peptide induces an oxidant stress in the cells. Overnight culture of cells with 10-20 microM beta-amyloid(25-35) induced apoptosis in SH-SY5Y cells when measured as externalization of phosphatidylserine by annexin V binding, as DNA fragmentation in the TUNEL assay, and as caspase-3 activity in cell lysates. Pre-loading cells with ascorbate substantially prevented apoptosis measured by these assays as well as cell death. In addition to preventing apoptosis, ascorbate loading of SH-SY5Y cells also decreased basal rates of generation of endogenous beta-amyloid. Together, these results support the notion that beta-amyloid induces apoptosis and death in neurons due to oxidant stress and suggest that intracellular ascorbate effectively prevents this toxicity.
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PMID:Ascorbic acid protects SH-SY5Y neuroblastoma cells from apoptosis and death induced by beta-amyloid. 1672 31

Cis-diamminedichloroplatinum (II) cisplatin (CDDP) is an organometallic compound frequently used in anti-cancer therapy, in particular ovarian, testicular, and head and neck tumors. We found cisplatin was effective against human promyelocytic leukemia cell line HL-60, inhibiting cell cycle progression and inducing time- and concentration- dependent cell death. Presence of nuclear fragmentation, caspase-3 cleavage and annexin V positivity suggests cell death occurred by apoptosis, although DNA internucleosomal fragmentation was not detected. In addition, analysis of malondialdehyde (MDA) production and protein carbonylation indicated that cisplatin increased lipid peroxidation and oxidation of cell proteins. This occurrence was prevented by antioxidants such as N-acetylcysteine (N-aC) and glutathione (GSH), which, consistently, were also able to prevent CDDP-induced cell death. Collectively, these findings indicate that, besides growth inhibition, an increase of oxygen radicals and lipid degradation can account for a significant part of CDDP-induced apoptosis.
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PMID:Cisplatin-induced apoptosis in human promyelocytic leukemia cells. 1686 38

This study was designed to investigate the apoptosis-inducing activity of delta-elemene on Hela cells in vitro. MTT assay and Hoechst 33258/PI fluorescence microscopy were used for this investigation. Apoptosis was further confirmed and quantified by DNA fragmentation ELISA, Annexin V (AnV) binding of externalized phosphatidylserine and the mitochondrial probe JC-1 using flow cytometry. Generation of reactive oxygen species (ROS) was detected using CM-H2DCFDA. Western blots analysis was performed using antibodies against the pro-caspase-3, or PRAP (Poly (ADP-ribose) polymerase). The results showed that delta-elemene exhibited a marked antiproliferative effect on Hela cells in dose- and time-dependent manners, and had little inhibition to normal human liver cell line WRL-68. It was demonstrated that delta-elemene was capable of inducing DNA fragmentation in a dose- and time-dependent manner. AnV positivity and the disturbance of the polarized mitochondrial transmembrane potential (Deltapsim) suggested that delta-elemene induced apoptotic death of Hela cells. Western blot analysis demonstrated that delta-elemene activated the caspase-signaling pathway, leading to the proteolysis conversion of pro-caspase-3 to activate caspase-3, and the subsequent cleavage of the caspase substrate PARP. Further, it was noted that the apoptotic effect of delta-elemene could be attenuated by L-Glutathione (GSH) or z-DEVD-fmk. It suggested that the increase in ROS generation might be involved in the mechanism of delta-elemene induced cell apoptosis.
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PMID:Effect of delta-elemene on Hela cell lines by apoptosis induction. 1701 27

Diabetes increases the percentage of circulating erythrocytes exposing phosphatidylserine (PS) at the cell surface. PS-exposing erythrocytes are recognized, bound, engulfed and degraded by macrophages. Thus, PS exposure, a feature of suicidal erythrocyte death or eryptosis, accelerates clearance of affected erythrocytes from circulating blood. Moreover, PS-exposing erythrocytes bind to the vascular wall thus interfering with microcirculation. The present study explored mechanisms involved in the triggering of PS exposure by methylgloxal, an extra- and intracellular metabolite which is enhanced in diabetes. PS exposure, cell size and cytosolic Ca(2+)-activity after methylglyoxal treatment were measured by FACS analysis of annexin V binding, forward scatter and Fluo-3-fluorescence, respectively, and it was shown that the treatment significantly enhanced the percentage of PS-exposing erythrocytes at concentrations (0.3 microM) encountered in diabetic patients. Surprisingly, methylglyoxal did not significantly increase cytosolic Ca(2+) concentration, and at concentrations up to 3 microM, did not decrease the forward scatter. Instead, exposure to methylglyoxal inhibited glycolysis thus decreasing ATP and GSH concentrations. In conclusion, methylglyoxal impairs energy production and anti-oxidative defense, effects contributing to the enhanced PS exposure of circulating erythrocytes and eventually resulting in anemia and deranged microcirculation.
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PMID:Stimulation of suicidal erythrocyte death by methylglyoxal. 1716 27

We investigated an involvement of ROS, such as H2O2 and O2- and GSH in the As4.1 cell death by antimycin A and examined whether ROS scavengers rescue antimycin A-induced As4.1 cell death and its mechanism. Levels of intracellular H2O2 and O2- were markedly increased in antimycin A-treated cells. Antimycin A reduced the intracellular GSH content. A ROS scavenger, Tiron down-regulated the production of intracellular H2O2. However, the reduction of intracellular H2O2 level did not change the apoptosis parameters, such as sub-G1 DNA content and annexin V binding. Interestingly, treatment of Tiron could partially prevent the loss of mitochondrial transmembrane potential (DeltaPsi(m)). Treatment of SOD and catalase also reduced the intracellular H2O2 and loss of mitochondrial transmembrane potential (DeltaPsi(m)) without reducing O2- level and apoptosis in antimycin A-treated As4.1 cells. All the ROS scavengers, SOD and catalase did not inhibit GSH depletion induced by antimycin A, resulting in failure of preventing the apoptosis. In addition, all the reagents including antimycin A did not induce any specific phase arrest of cell cycle in As4.1 cells. In summary, these results demonstrate that antimycin A generates potently ROS, H2O2 and O2- and induces the depletion of GSH content in As4.1 JG cells, and that Tiron, SOD and catalase inhibited partially the loss of mitochondrial transmembrane potential (DeltaPsi(m)) via the reduction of intracellular H2O2 level.
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PMID:The changes of intracellular H2O2 are an important factor maintaining mitochondria membrane potential of antimycin A-treated As4.1 juxtaglomerular cells. 1717 41

Antimycin A (AMA), an inhibitor of electron transport in mitochondria, has been used as a reactive oxygen species (ROS) generator in biological systems. Here, we investigated the in vitro effect of AMA on apoptosis in HeLa cells. AMA inhibited the growth of HeLa cells with an IC(50) of about 50 microM. AMA efficiently induced apoptosis, as evidenced by flow cytometric detection of sub-G1 DNA content, annexin V binding assay, and DAPI staining. This apoptotic process was accompanied by the loss of mitochondrial membrane potential (DeltaPsi(m)), Bcl-2 down-regulation, Bax up-regulation, and PARP degradation. All caspase inhibitors used in this experiment, especially pan-caspase inhibitor (Z-VAD), could rescue some HeLa cells from AMA-induced cell death. When we examined the changes of the ROS, H(2)O(2) or O(2) (.-), in AMA-treated cells, H(2)O(2) and O(2) (.-) were markedly increased. In addition, we detected the depletion of GSH content in AMA-treated cells. Pan-caspase inhibitor showing the efficient anti-apoptotic effect significantly reduced GSH depletion by AMA. Superoxide dismutase (SOD) and catalase did not reduce intracellular ROS, but these could strongly rescue the cells from apoptosis. However, these anti-apoptotic effects were not accompanied by the recovery of GSH depletion. Interestingly, catalase significantly decreased the CMF negative (GSH depletion) and propidium iodide (PI) positive cells, indicating that catalase strongly maintained the integrity of the cell membrane in CMF negative cells. Taken together, these results demonstrate that AMA potently generates ROS, induces the depletion of GSH content in HeLa cells, and strongly inhibits the growth of HeLa cells throughout apoptosis.
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PMID:An ROS generator, antimycin A, inhibits the growth of HeLa cells via apoptosis. 1737 17

We investigated the involvement of ROS such as H2O2 and O2*-, and GSH in As4.1 cell death induced by pyrogallol. The intracellular H2O2 levels were decreased or increased depending on the concentration and incubation time of pyrogallol. The levels of O2*- were significantly increased. Pyrogallol reduced the intracellular GSH content. And ROS scavengers, Tempol, Tiron, Trimetazidine and NAC could not significantly down-regulate the production of H2O2 and O2*-. However, these ROS scavengers slightly inhibited apoptosis. Interestingly, Tempol showing the recovery of GSH depletion induced by pyrogallol significantly decreased apoptosis without the significant reduction of intracellular O2*- levels. SOD and catalase did not change the level of H2O2 but decreased the level of O2*-. The inhibition of GSH depletion by these was accompanied with the decrease of apoptosis, as evidenced by sub-G1 DNA content, annexin V staining, mitochondria membrane potential (DeltaPsi(m)) and Western data. In addition, ROS scavengers and SOD did not alter a G2 phase accumulation of the cell cycle induced by pyrogallol. However, catalase changed the cell cycle distributions of pyrogallol-treated cells to those of pyrogallol-untreated cells. In summary, we have demonstrated that pyrogallol potently generates ROS, especially O2*-, in As4.1 JG cells, and Tempol, SOD and catalase could rescue to a lesser or greater extent cells from pyrogallol-induced apoptosis through the up-regulation of intracellular GSH content.
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PMID:A superoxide anion generator, pyrogallol induces apoptosis in As4.1 cells through the depletion of intracellular GSH content. 1738 55


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