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)

The mechanisms of catechol-induced cytotoxicity were studied in cultures of neuroblastoma N2a cells. The minimal cytotoxic concentration after 72 h was 20 micromol x l(-1). The EC50 after 72 h was 38 micromol x l(-1). There was not a correlation between the cytotoxicity and the formation of quinones in the medium. Catechol-induced cytotoxicity was increased significantly when superoxide dismutase (SOD) was added. The addition of catalase did not protect cells, but this enzyme reverted the deleterious effect of SOD. The experimental studies showed a detrimental effect of deferoxamine on catechol-induced cytotoxicity suggesting that cells need iron to maintain its metabolism. NF-kappaB inhibitors increased the cytotoxicity, suggesting that this factor is also important for cell viability. L-cysteine and N-acetyl-L-cysteine protected cells significantly in a dose-dependent manner. The use of monochlorobimane showed that catechol induced reduced glutathione (GSH) depletion after 24 h, prior to cell death. The mode of cell death was studied by flow cytometry after double staining with annexin V and propidium iodide. Catechol induced apoptosis after 72 h. Furthermore, catechol also induced nuclear fragmentation. These data showed that catechol-induced cytotoxicity to N2a cell was not directly a consequence of reactive oxygen species production. Rather, it was due to GSH depletion followed by the induction of apoptosis.
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PMID:Cytotoxic effects of catechol to neuroblastoma N2a cells. 1920 5

Pyrogallol (PG) is a polyphenol compound and has been known to be an O(2)(*-) generator. We evaluated the effects of PG on the growth of human pulmonary A549 cells in relation to the cell cycle and apoptosis. Treatment with 50 or 100 microM PG significantly inhibited the cell growth of A549 for 72 h. DNA flow cytometric analysis indicated that PG slightly induced a G1 phase arrest of the cell cycle at 24 or 48 h, but did not induce the specific cell cycle arrest at 72 h. Intracellular GSH depletion was observed in PG-treated cells. PG induced apoptosis in A549 cells, as evidenced by sub-G1 cells, annexin V staining cells, and the loss of mitochondrial membrane potential (DeltaPsi(m)). The intracellular ROS (reactive oxygen species) level including O(2)(*-) increased in PG-treated A549 cells at 24 and 48 h, and persisted at 72 h. The changes in GSH as well as ROS levels by PG affected the cell viability in A549 cells. In conclusion, PG inhibited the growth of human pulmonary A549 cells by inducing cell cycle arrest as well as triggering apoptosis.
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PMID:Pyrogallol inhibits the growth of human pulmonary adenocarcinoma A549 cells by arresting cell cycle and triggering apoptosis. 1920 62

Propyl gallate (PG) as a synthetic antioxidant is widely used in processed food, cosmetics and medicinal preparations. Despite the assumed low toxicity of PG, it exerts a variety of effects on tissue and cell functions. In the present study, we evaluated the anti-apoptotic effects of caspase inhibitors on PG-treated human cervix adenocarcinoma HeLa cells in relation to the changes of reactive oxygen species (ROS) and glutathione (GSH) levels. PG induced apoptosis in a dose-dependent manner, as evidenced by sub-G1 cells and annexin V staining cells. Treatment with pan-caspase inhibitor, caspase-3 inhibitor, caspase-8 inhibitor or caspase-9 inhibitor significantly prevented apoptosis in PG-treated HeLa cells at 24 h. The intracellular ROS levels including O (2) (*-) were increased or decreased in PG-treated HeLa cells depending on the incubation times (1 or 24 h). PG depleted intracellular GSH content in HeLa cells at 24 h. Treatment with caspase inhibitor reduced ROS levels and significantly prevented GSH depletion in PG-treated HeLa cells at 24 h. In conclusion, PG induced apoptosis in HeLa cells. The anti-apoptotic effect of caspase inhibitor on PG-induced HeLa cell death was closely related to the reduction of ROS levels, especially mitochondrial O (2) (*-) , as well as to the inhibition of GSH depletion.
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PMID:The anti-apoptotic effects of caspase inhibitors on propyl gallate-treated HeLa cells in relation to reactive oxygen species and glutathione levels. 1943 96

MG132 (carbobenzoxy-Leu-Leu-leucinal) is a peptide aldehyde, which effectively blocks the proteolytic activity of the 26S proteasome complex. We evaluated the effects of MG132 on the growth of human cervix cancer HeLa cells in relation to the cell growth, reactive oxygen species (ROS) and glutathione (GSH) levels. Dose-dependent inhibition of cell growth was observed in HeLa cells with an IC50 of approximately 5 microM MG132 for 24 h. DNA flow cytometric analysis indicated that treatment with MG132 induced S, G2-M or non-specific phase arrests of the cell cycle dose-dependently. Treatment with MG132 induced apoptosis in a dose-dependent manner, as evidenced by sub-G1 cells and annexin V staining cells. Treatment with MG132 also induced the loss of mitochondrial membrane potential in HeLa cells. The intracellular ROS levels including O2*- were significantly increased in MG132-treated cells. Furthermore, the depletion of intracellular GSH content was observed in cells treated with MG132. In conclusion, MG132 inhibited the growth of HeLa cells via inducing the cell cycle arrest as well as triggering apoptosis. The changes of ROS and GSH by MG132 were closely related to apoptosis in HeLa cells.
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PMID:The effect of MG132, a proteasome inhibitor on HeLa cells in relation to cell growth, reactive oxygen species and GSH. 1951 26

Three extracts of defatted seeds of Oenothera paradoxa Hudziok, aqueous extract, 60% ethanolic extract, and 30% isopropanolic extract, differing by their total content of phenolic compounds and by their contents of individual polyphenols, were investigated in this study. The extracts exerted cytotoxic action on HTB-140 human skin melanoma cells. After 24 h of incubation, IC(50) values of 169.7 +/- 5.9 micog/mL, 72.4 +/- 3.8 microg/mL, and 155.3 +/- 6.3 microg/mL were obtained for HTB-140 cells with the aqueous extract, 60% ethanolic extract, and 30% isopropanolic extract at the tested concentrations (5-200 microg/mL), respectively, while IC(50) for normal fibroblast cells NHDFs was not attained. Moreover, for HTB-140 cells, LD(50) (concentration at which 50% of cells were dead) of 89.2 +/- 4.3 microg/mL and 181.4 +/- 6.5 microg/mL were obtained with 60% ethanolic extract and 30% isopropanolic extract, respectively. In melanoma cells, all three extracts caused a concentration-dependent increase of ROS production, GSH, and ATP lowering, and appearance of phosphatidylserine on the external surface of cellular membranes where it was bound to annexin V-FITC; furthermore, apoptosis without activation of caspase-3 took place. The most effective was 60% ethanolic extract, which had the greatest total content of phenolic compounds and the greatest content of pentagalloyloglucose (PGG).
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PMID:Pro-oxidative and pro-apoptotic action of defatted seeds of Oenothera paradoxa on human skin melanoma cells. 1969 34

Endothelial progenitor cells (EPCs) play an important role in preventing atherosclerosis. The factors that regulate the function of EPCs are not completely clear. Increased formation of advanced glycation endproducts (AGEs) is generally regarded as one of the main mechanisms responsible for vascular damage in patients with diabetes and atherosclerosis. AGEs lead to the generation of reactive oxygen species (ROS) and part of the regenerative capacity of EPCs seems to be due to their low baseline ROS levels and reduced sensitivity to ROS-induced cell apoptosis. Therefore, we tested the hypothesis that AGEs can alter functions and promote apoptosis in EPCs through overpress cell oxidant stress. EPCs, isolated from bone marrow, were cultured in the absence or presence of AGEs (50, 100, and 200 microg/ml). A modified Boyden's chamber was used to assess the migration of EPCs and the number of recultured EPCs was counted to measure the adhesiveness function. MTT assay was used to determine the proliferation function. ROS were analyzed using the ROS assay kit. A spectrophotometer was used to assess superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity, and PCR was used to test mRNA expression of SOD and GSH-PX. SiRNA was used to block receptor for advanced glycation endproducts (RAGEs) expression. Apoptosis was evaluated by Annexin V immunostaining and TUNEL staining. Co-culturing with AGEs increases ROS production, decreases anti-oxidant defenses, overpresses oxidant stress, inhibits the proliferation, migration, and adhesion of EPCs, and induces EPCs apoptosis. In addition, these effects were attenuated during block RAGE protein expression by siRNA. AGEs may serve to impair EPCs functions through RAGE-mediate oxidant stress, and promote EPCs sensitivity toward oxidative-stress-mediated apoptosis, which indicates a new pathophysiological mechanism of disturbed vascular adaptation in atherosclerosis and suggests that lower levels of AGEs might improve the success of progenitor cell therapy.
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PMID:Advanced glycation endproducts alter functions and promote apoptosis in endothelial progenitor cells through receptor for advanced glycation endproducts mediate overpression of cell oxidant stress. 1975 58

Carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP) is an uncoupler of mitochondrial oxidative phosphorylation in eukaryotic cells. Here, we evaluated the in vitro effects of FCCP on the growth of Calu-6 lung cancer cells. FCCP inhibited the growth of Calu-6 cells with an IC(50) of approximately 6.64+/-1.84 microM at 72 h, as shown by MTT. DNA flow cytometric analysis indicated that FCCP induced G1 phase arrest below 20 microM of FCCP. Treatment with FCCP decreased the level of CDKs and cyclines in relation to G1 phase. In addition, FCCP not only increased the p27 level but also enhanced its binding with CDK4, which was associated with hypophosphorylation of Rb protein. While transfection of p27 siRNA inhibited G1 phase arrest in FCCP-treated cells, it did not enhance Rb phosphorylation. FCCP also efficiently induced apoptosis. The apoptotic process was accompanied with an increase in sub-G1 cells, annexin V staining cells, mitochondria membrane potential (MMP) loss and cleavage of PARP protein. All of the caspase inhibitors (caspase-3, -8, -9 and pan-caspase inhibitor) markedly rescued the Calu-6 cells from FCCP-induced cell death. However, knock down of p27 protein intensified FCCP-induced cell death. Moreover, FCCP induced the depletion of GSH content in Calu-6 cells, which was prevented by all of the caspase inhibitors. In summary, our results demonstrated that FCCP inhibits the growth of Calu-6 cells in vitro. The growth inhibitory effect of FCCP might be mediated by cell cycle arrest and apoptosis via decrease of CDKs and caspase activation, respectively. These findings now provide a better elucidation of the mechanisms involved in FCCP-induced growth inhibition in lung cancer.
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PMID:Effects of carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone on the growth inhibition in human pulmonary adenocarcinoma Calu-6 cells. 1981 88

Ionizing radiation (IR) is a pro-oxidant that kills cells by both apoptotic and necrotic mechanisms. Pyrrolidine dithiocarbamate (PDTC) is a thiol-containing compound that may act either as a pro- or anti-oxidant depending on the experimental conditions. This study was designed to determine whether PDTC would reduce or enhance IR-induced cell death of freshly-isolated normal mouse B6/129 spleen cells (NMSC). We determined the effect of increasing doses of IR, PDTC alone and PDTC followed by IR on the viability of NMSC. Annexin V and propidium iodide (Annexin V/PI) staining demonstrated a dose and time-dependent relationship in which PDTC enhanced the percentage of IR-induced apoptotic/necrotic NMSC. Trypan blue dye inclusion confirmed that a loss of membrane integrity was occurring 1 h after incubation with PDTC plus IR. Reduction in the glutathione (GSH)/glutathione disulfide (GSSG) ratio and GSH demonstrated that both IR (8.5 Gy) and PDTC acted as pro-oxidants, but their mechanisms of action differed: In contrast to IR, which promoted p53 activation and caspase 3/7-mediated apoptosis, PDTC inhibited IR-induced p53 and caspase 3/7 activity. However, PDTC increased H(2)O(2) formation and necrosis, resulting in an overall increase in IR-induced cell death. Catalase prevented the PDTC-induced increase in IR cytotoxicity implicating the generation of H(2)O(2) as a major factor in this mechanism. These results demonstrate that in NMSC PDTC acts as pro-oxidant and enhances IR-induced cell cytotoxicity by increasing H(2)O(2)formation and thiol oxidation. As such, they strongly suggest that the use of PDTC as an adjunct to reduce radiation toxicity should be avoided.
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PMID:Pyrrolidine dithiocarbamate (PDTC) blocks apoptosis and promotes ionizing radiation-induced necrosis of freshly-isolated normal mouse spleen cells. 2033 68

Methylglyoxal (MG), a reactive dicarbonyl produced during glucose metabolism, is found at high levels in the blood of diabetic patients. MG induces oxidative stress and apoptosis. There is evidence that MG causes glutathione (GSH) depletion. However, it remains unknown whether GSH plays a protective role against the cytotoxic effect of MG. We examined the effect of DL-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione (GSH) biosynthesis, on the viability of bovine aortic endothelial cells (BAECs) exposed to MG. BAECs pretreated with BSO showed reduced ability to survive MG exposure. Flow cytometric analyses with annexin V and propidium iodide double staining revealed that BAECs exposed to MG after BSO pretreatment displayed features characteristic of apoptosis. Caspase-3 activation induced by MG was increased by BSO. Moreover, measurement of protein carbonyl levels showed that BSO promoted MG-induced oxidative stress. Taken together, these findings suggest that the depletion of GSH via BSO pretreatment promoted MG-induced apoptotic cell death and oxidative stress in BAECs.
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PMID:Buthionine sulfoximine promotes methylglyoxal-induced apoptotic cell death and oxidative stress in endothelial cells. 2041 May 85

MG132 as a proteasome inhibitor can induce apoptotic cell death through formation of reactive oxygen species (ROS). In this study, the effects of N-acetyl cysteine (NAC; an antioxidant) on MG132-induced HeLa cell death in relation to ROS and glutathione (GSH) were investigated. MG132 induced cell growth inhibition and apoptosis in HeLa cells, which was accompanied by the loss of mitochondrial membrane potential (MMP; Delta Psi(m)), activation of caspase-3 and poly (ADP-ribose) polymerase (PARP) cleavage. MG132 increased ROS levels, including O(2)(*-), and GSH depleted cell numbers of HeLa cells. NAC reduced the number of annexin V-positive cells and MMP (Delta Psi(m)) loss by MG132. In addition, NAC significantly reduced the ROS level and prevented GSH depletion. In conclusion, NAC prevented MG132-induced HeLa cell death via decreasing ROS and preventing GSH depletion.
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PMID:Attenuation of MG132-induced HeLa cell death by N-acetyl cysteine via reducing reactive oxygen species and preventing glutathione depletion. 2065 58


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