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)

Parviflorene F (1), a novel sesquiterpenoid dimer isolated from Curcuma parviflora Wall, is a cytotoxic compound. In this study, we examined the mechanism of its cytotoxic effect in HeLa cells. Treatment with 1 enhanced the mRNA and protein expression of TRAIL-R2 (tumor necrosis factor alpha-related apoptosis inducing ligand receptor 2). Apoptosis was induced by 1 as revealed by the distribution of DNA and Annexin V/PI staining using flow cytometry. In addition, 1-induced apoptosis was inhibited by human recombinant TRAIL-R2/Fc chimera protein, TRAIL-neutralizing fusion protein. Also, we found that 1 induced the activation of caspase-8, caspase-9, and caspase-3, indicating that the cytotoxic effect of 1 is correlated with apoptosis by a caspase-dependent mechanism through TRAIL-R2. In addition, 1 enhanced TRAIL-induced cell death against HeLa and TRAIL-resistant DLD1 cells. Taken together, up-regulation of TRAIL-R2 by 1 may contribute to sensitization of TRAIL-induced cell death.
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PMID:A novel sesquiterpenoid dimer parviflorene F induces apoptosis by up-regulating the expression of TRAIL-R2 and a caspase-dependent mechanism. 1803 20

Photodynamic therapy (PDT) is an alternative anticancer treatment in which direct tumor-cell killing results from selective accumulation of photosensitizers in the tumor sites and phototoxicity occurs when light-activated photosensitizers transfer the energy to oxygen nearby to produce singlet oxygen. The objective of this study was to investigate the effects of PDT using chlorophyll derivatives such as pheophytin a (phe a), pheophytin b (phe b), pheophorbide a (pho a) and pheophorbide b (pho b) as the photosensitizers, and the 660 nm light-emitting diodes (LEDs) irradiation on human hepatocellular carcinoma cells (HuH-7). The drug concentration-dependent inhibition of HuH-7 cell viability was studied under LEDs irradiation (10 mW cm(-2)) at radiant exposure of 5.1 and 10.2 J cm(-2) by MTT assay. Significant inhibition of the survival of HuH-7 cells (<10%) was observed when an irradiation dose of 10.2 J cm(-2) combined with the concentration of 0.5 microg ml(-1) of phe a, 0.125 microg ml(-1) of pho a, 0.25 microg ml(-1) of phe b, and 0.125 microg ml(-1) of pho b were applied. The results from Annexin V-propidium iodide staining revealed that phe a, phe b, pho a and pho b could induce cell death in HuH-7 cells predominantly via a necrotic process. The results from immunoblot analyses exhibited that chlorophyll derivative-mediated PDT initiated cytochrome c release, caspase-9 and caspase-3 activation, followed by poly ADP-ribose polymerase (PARP) cleavage. Thus, apoptosis also occurred in HuH-7 cells after PDT treatment, and the execution of the apoptotic process may be initiated from the loss of mitochondrial function. Our findings demonstrate that both apoptosis and necrosis can be induced in HuH-7 cells after PDT using phe a, phe b, pho a and pho b and LEDs.
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PMID:A study on the photodynamic properties of chlorophyll derivatives using human hepatocellular carcinoma cells. 1804 91

To investigate the correlation between sensitivity to Fas ligand (FasL) and expression level of decoy receptor 3 (DcR3) on tumor cell surface, Fas/DcR3 mRNA expression was detected by RT-PCR. Anti-DcR3 mAb was used to detect expression level of DcR3 on surface of tumor cells by flow cytometry. Caspase-8, caspase-9, caspase-3, Bcl-2 expressions were analyzed by Western blot, respectively. Sensitivity to apoptosis induced by FasL was determined by Annexin V apoptosis kit. The expressions of DcR3 on the surface of tumor cells from high to low were approximately 35.3% in BGC823 cells, and 21.6% in MCF-7 cells, respectively. The apoptotic rates induced by FasL from low to high were 15.6% in BGC823 cells, and 58.2% in MCF-7 cells, respectively. There was a significant correlation between the expression levels of DcR3 with FasL-inducing apoptosis.
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PMID:Correlation between expression of DcR3 on tumor cells and sensitivity to FasL. 1816 57

The cell survival activity of human glioma cells is largely dependent on autocrine fibroblast growth factor (FGF) signaling. Caspases, a family of cysteine proteases, play an integral part in the execution phase of apoptosis. To better understand the mechanism of resistance to apoptosis in human glioma cells, we investigated the effect of a blockade of endogenous FGF signaling through the expression of the dominant negative type I FGF receptor (DNFGFR) in U251MG cells. The cells were infected with adenovirus vector expressing DNFGFR (AdDNFGFR) and apoptosis was semi-quantified by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method and flow cytometric annexin V assay. The activation of caspase-3, -8, and -9, the activation of Akt, a serine/threonine protein kinase, and the cleavage of poly(ADP-ribose) polymerase (PARP) were analyzed by immunoblotting. The infection with AdDNFGFR (multiplicity of infection of 200) induced marked apoptosis, along with a down-regulation of akt phosphorylation, and activation of caspase-9 and -3, but not -8. By contrast, LacZ virus (a control) had minimal effects. The level of the cleaved form of PARP was increased in a time-dependent fashion, and this increase was inhibited by adding Z-DEVD-FMK, a caspase-3 inhibitor, and Z-LEHD-FMK, a caspase-9 inhibitor. Moreover, ultraviolet exposure (100 J/m(2)) induced apoptosis and caspase-8, but not caspase-9, activation. Our data suggested that the induction of apoptosis through the inhibition of endogenous FGF signaling is caspase-9 pathway- dependent. The suppression of this or other specific anti-apoptotic pathways may lead to genetic or pharmacological manipulations that favorably modulate the malignant behavior of human gliomas.
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PMID:Caspase-9 pathway activation by inhibiting endogenous fibroblast growth factor signaling in human glioma cells. 1820 70

The nephrotoxicity of diclofenac, a non-steroidal anti-inflammatory drug that inhibits both isoforms of cyclooxygenase (COX) has been reported to be fatal to vultures but this was not so with meloxicam which is COX-2 selective. Our study showed that diclofenac was more toxic than meloxicam to both the proximal tubular LLC-PK1 cells and the distal tubular Madin-Darby canine kidney type II (MDCKII) cells, and that LLC-PK1 cells were more susceptible. Exposure of MDCKII cells to meloxicam caused activation of caspase-9/-3 and release of cytochrome c. These observations together with a positive annexin V-FITC staining implicate an intrinsic mitochondrial cell death pathway by apoptosis. Diclofenac-treated MDCKII cells on the other hand showed extensive propidium iodide staining, suggestive of cell death by necrosis. The mode of cell death in LLC-PK1 cells was however less well-defined with positive annexin V-FITC staining but minimal increase in caspase-3 activity alluding to a caspase-independent pathway.
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PMID:Nephrotoxic cell death by diclofenac and meloxicam. 1832 23

A quaternary benzo[c]phenanthridine alkaloid chelerythrine displays a wide range of biological activities including cytotoxicity to normal and cancer cells. In contrast, less is known about the biological activity of dihydrochelerythrine, a product of chelerythrine reduction. We examined the cytotoxicity of chelerythrine and dihydrochelerythrine in human promyelocytic leukemia HL-60 cells. After 4h of treatment, chelerythrine induced a dose-dependent decrease in the cell viability with IC50 of 2.6 microM as shown by MTT reduction assay. Dihydrochelerythrine appeared to be less cytotoxic since the viability of cells exposed to 20 microM dihydrochelerythrine for 24h was reduced only to 53%. Decrease in the viability induced by both alkaloids was accompanied by apoptotic events including the dissipation of mitochondrial membrane potential, activation of caspase-9 and -3, and appearance of cells with sub-G1 DNA. Moreover, chelerythrine, but not dihydrochelerythrine, elevated the activity of caspase-8. A dose-dependent induction of apoptosis and necrosis by chelerythrine and dihydrochelerythrine was confirmed by annexin V/propidium iodide dual staining flow cytometry. Besides, both alkaloids were found to induce accumulation of HL-60 cells in G1 phase of the cell cycle. We conclude that both chelerythrine and dihydrochelerythrine affect cell cycle distribution, activate mitochondrial apoptotic pathway, and induce apoptosis and necrosis in HL-60 cells.
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PMID:Chelerythrine and dihydrochelerythrine induce G1 phase arrest and bimodal cell death in human leukemia HL-60 cells. 1835 94

We previously identified and characterized a murine BTB domain-containing protein, CIBZ (ZBTB38 in human), that interacts with CtBP and binds to methylated CpGs. However, its physiological function remained unknown. As CtBP is reportedly involved in p53-independent programmed cell death, we examine here whether CIBZ is associated with apoptosis. We found that CIBZ was highly expressed in proliferating C2C12 cells but that its expression levels decreased upon induction of apoptosis by serum starvation. Knockdown of CIBZ by small interfering RNA in C2C12 cells induced apoptosis, as determined by an increase of annexin V/propidium iodide labeling, activation of caspase-3, and cleavage of poly(ADP-ribose) polymerase. CIBZ inhibition also activated caspase-7 and caspase-9, suggesting that CIBZ-associated apoptosis occurs through the mitochondrial pathway. Notably, knockdown of CIBZ in p53(-/-) mouse embryonic fibroblast cells also activated caspase-3 and cleavage of poly(ADP-ribose) polymerase, indicating that CIBZ-associated apoptosis is mediated by a p53-independent pathway; however, because both common and distinct targets are regulated by CIBZ- and CtBP-associated apoptosis, we conclude that more than one pathway is involved. Finally, using mutagenesis and an in vitro caspase cleavage assay, we show that CIBZ is a novel substrate of caspase-3 and identify two caspase-3 recognition sites. These findings indicate, collectively, that CIBZ plays an important role by participating in the negative regulation of apoptosis in murine cells.
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PMID:Down-regulation of CIBZ, a novel substrate of caspase-3, induces apoptosis. 1837 81

Glycogen storage disease type Ib (GSD-Ib) is caused by a deficiency in the glucose-6-phosphate (G6P) transporter (G6PT) that works with a liver/kidney/intestine-restricted glucose-6-phosphatase-alpha (G6Pase-alpha) to maintain glucose homeostasis between meals. Clinically, GSD-Ib patients manifest disturbed glucose homeostasis and neutrophil dysfunctions but the cause of the latter is unclear. Neutrophils express the ubiquitously expressed G6PT and G6Pase-beta that together transport G6P into the endoplasmic reticulum (ER) lumen and hydrolyze it to glucose. Because we expected G6PT-deficient neutrophils to be unable to produce endogenous glucose, we hypothesized this would lead to ER stress and increased apoptosis. Using GSD-Ib mice, we showed that GSD-Ib neutrophils exhibited increased production of ER chaperones and oxidative stress, consistent with ER stress, increased annexin V binding and caspase-3 activation, consistent with an increased rate of apoptosis. Bax activation, mitochondrial release of proapoptotic effectors, and caspase-9 activation demonstrated the involvement of the intrinsic mitochondrial pathway in these processes. The results demonstrate that G6P translocation and hydrolysis are required for normal neutrophil functions and support the hypothesis that neutrophil dysfunction in GSD-Ib is due, at least in part, to ER stress and increased apoptosis.
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PMID:Neutrophil stress and apoptosis underlie myeloid dysfunction in glycogen storage disease type Ib. 1842 Aug 28

20-Hydroxyeicosatetraenoic acid (20-HETE), a omega-hydroxylation product of arachidonic acid catalyzed by cytochrome P450 4A (CYP4A), plays a role in vascular smooth muscle remodeling. Although its effects on angiogenic responses are known, it remains unclear whether 20-HETE acts on apoptosis of pulmonary arterial smooth muscle cells (PASMC), an important step in PASMC remodeling, and what pathways are involved in the process. Here we show evidence for the missing information. The effect of 20-HETE on PASMC apoptosis and the apoptosis-associated signaling pathways were determined with cell viability assay, Annexin V and propidium idodide binding, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), mitochondrial potentials assay, caspase activity assay and Western blots. We found that exogenous 20-HETE suppressed the serum deprivation-induced loss of bovine PASMCs and prevented Annexin V binding, DNA nick end labeling and chromatin condensation. The effect was worsened by 17-octadecynoic acid (17-ODYA), which inhibited the production of endogenous 20-HETE. Furthermore, 20-HETE induced the expression of bcl-2, maintained the stability of mitochondria membrane, and relieved the activation of caspase-9 and caspase-3. Such effects were reversed in the presence of 17-ODYA. Thus, these findings indicate that 20-HETE protects PASMCs against apoptosis by acting on, at least in part, the intrinsic apoptotic pathway.
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PMID:20-Hydroxyeicosatetraenoic acid inhibits the apoptotic responses in pulmonary artery smooth muscle cells. 1845 23

The cell proliferation of p53-deficient Jurkat T cells is controlled after prolonged exposure to human lactoferrin (Lf). However, the molecular mechanism by which Lf influences these cellular responses remains unclear. In this study, we demonstrate that Lf-induced apoptosis in Jurkat T cells occurs in a dose- and time-dependent manner via the regulation of c-Jun N-terminal kinase (JNK) activity. Jurkat cells exposed to Lf for 1 day, especially at concentrations in excess of 500 microg/ml, showed typical apoptosis, as indicated by decreased cell viability and increased Annexin V binding. Our results also showed that Lf induced the activation of caspase 9 and caspase 3 activation, as demonstrated by our detection of cleaved caspases and PARP. Lf-induced apoptosis did not influence Bcl-2 expression via an ERK1/2 phosphorylation pathway, but was rather associated with the level of Bcl-2 phosphorylation. The treatment of cells with the specific JNK inhibitor SP600125, but not the p38 MAPK inhibitor SB203580, revealed that the JNK-Bcl-2 signaling cascade is required for Lf-induced apoptosis. When JNK activation was abolished by SP600125, no Bcl-2 phosphorylation was detected, and the Lf-treated Jurkat cells did not undergo cell death. These findings indicate that Lf functions as a biological mediator of apoptosis in the human leukemia Jurkat T-cell line, via the JNK-associated Bcl-2 signaling pathway.
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PMID:Requirement of the JNK-associated Bcl-2 pathway for human lactoferrin-induced apoptosis in the Jurkat leukemia T cell line. 1853 98


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