Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.22.56 (caspase-3)
35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic ischemia reperfusion (HIR) not only results in liver injury, but also leads to endotoxemia, which aggravates HIR-induced liver injury and dysfunction, or even causes liver failure. Taurine has been shown to protect organs from ischemia reperfusion or endotoxin by its anti-oxidant and anti-inflammatory activities. The aim of this study was to investigate whether taurine could attenuate endotoxin-induced acute liver injury after HIR. Wistar rats subjected to 30 min of hepatic ischemia followed by reperfusion and lipopolysaccharide (LPS) (0.5 mg/kg) administration, exhibited liver dysfunction (elevated serum levels of ALT, AST and LDH) and hepatic histopathological alteration. The serum levels of TNF-alpha and production of myeloperoxidase (MPO) and malondialdehyde (MDA) in liver tissues and apoptosis of hepatocytes were also increased after the combination of HIR and LPS. However, pre-administration of taurine protected livers from injury induced by the combination of HIR + LPS as the histological score, apoptotic index, MPO activity and production of MDA in liver tissues, and serum levels of AST, ALT, LDH and TNF-alpha, were significantly reduced. The expression of caspase-3, Fas and Fas ligand was upregulated in homogenates of livers from rats subjected to HIR and LPS, and this elevated expression could be inhibited by taurine. In summary, the results further emphasize the potential utilization of taurine in protecting livers against endotoxin-induced injury especially after HIR, by its anti-inflammatory, anti-oxidative and anti-apoptotic activities.
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PMID:Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion. 1926 95

T-2 toxin belongs to the large group of trichothecene mycotoxins synthesized by various Fusarium molds which can infect raw agriculture materials. Among the trichothecenes, T-2 toxin is one of the most potent mycotoxins and poses a potential health risk in human nutrition. Several acute and chronic toxic effects were observed in humans after consumption of contaminated food. Due to the rapid metabolism of T-2 toxin by esterases, several metabolites can be found in food and also in vivo after ingestion. The aim of this work was to determine the effects of T-2 toxin and of several of its metabolites, namely HT-2 toxin, neosolaniol, T-2-triol and T-2 tetraol, on two human cells in primary culture: human renal proximal tubule epithelial cells (RPTEC) and normal human lung fibroblasts (NHLF). Concerning the cytotoxicity of T-2 toxin and its metabolites, different studies were performed with animal cells and cell lines but there are only little data about cytotoxic effects in human cells. The use of human cells in primary culture gives a good completion of the already known data because these might be limited due to the disadvantages of cell lines (e.g., immortalization, tumor derivation, longtime cultivation). In order to study the cytotoxicity and mode of cell death, the parameters cell viability, caspase-3-activity and LDH-release were measured after exposure to T-2 toxin and several of its metabolites. With IC(50) values of 0.2 and 0.5 microM T-2 toxin showed the strongest cytotoxic effect in both cells with triggering apoptosis as kind of cell death starting at a concentration of 100nM. The metabolites HT-2 toxin and neosolaniol revealed weaker cytotoxic effects (IC(50): 0.7-3.0 microM) and induced apoptosis at higher concentrations (>1 microM). The other metabolites were less cytotoxic (IC(50): 8.3-25.1 microM) and did not activate caspase-3. In addition to the analysis of cytotoxic effects, we also studied the metabolism of T-2 toxin in these cells in primary culture. Using LC-ESI-MS/MS we could demonstrate that both cells are able to transform T-2 toxin into HT-2 toxin. Further metabolic activity could only be observed in renal proximal tubule (RPTEC) cells by forming neosolaniol as a second metabolite.
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PMID:Metabolism and cytotoxic effects of T-2 toxin and its metabolites on human cells in primary culture. 1942 30

The purpose of the current study is to understand the effects of nicotine in human retinal pigment epithelial (ARPE-19), human microvascular endothelial cells (HMVEC) and rat neurosensory retinal (R28) cells. ARPE-19, HMVEC and R28 cell cultures were treated with 10(-2) and 10(-4)M nicotine for 24h. R28 cells were also pre-treated for 4h with ALLN and ALLM (calpain inhibitors) or epicatechin, an antioxidant flavonoid compound. Trypan blue dye exclusion assay, caspase-3/7, LDH activity and DNA laddering assays were performed. With 10(-2)M nicotine treatment, R28 cell cultures showed decreased cell viability that was partially reversed by pre-treatment with the antioxidant epicatechin but not with calpain inhibitors. The DNA ladder assay showed a 200bp banding pattern consistent with apoptosis, however, caspase-3/7 activity was not increased. After treatment with 10(-2)M nicotine, HMVEC cultures showed decreased cell viability and increased LDH activity but no DNA banding patterns or caspase-3/7 activity. ARPE-19 cells showed no change in cell viability or caspase-3/7 activity at any of the nicotine concentrations. We conclude of dissimilar responses to nicotine treatment in three different cell lines. Nicotine was toxic to HMVEC and R28 cell cultures but the ARPE-19 cells were unaffected. In R28 cells, the nicotine effects were through an oxidant pathway that is non-caspase, non-calpain mediated while the HMVEC toxicity was via necrosis. Understanding the mechanisms of cell death may have potential therapeutic implications in the treatment of cigarette smoking related retinal diseases such as age-related macular degeneration (AMD).
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PMID:Differential effects of nicotine on retinal and vascular cells in vitro. 1942 45

The mechanisms of protective effect of N-methyl-D-aspartate (NMDA) receptor stimulation on apoptosis of neurons at their early stage of development are poorly understood. In the present study, we investigated the effects of NMDA on staurosporine (St)- and low-potassium (LP)-evoked apoptotic cell death in primary cerebellar granule cell (CGC) cultures at 7 days in vitro (DIV). We found that NMDA (200 microM) attenuated the St (0.5 microM)- and LP (5 mM KCl)-induced neuronal cell death in 7 but not 12 DIV CGC as confirmed by LDH release and MTT reduction assays. Moreover, NMDA attenuated St-and LP-evoked DNA fragmentation and cytosolic apoptosis inducing factor (AIF) protein level but not caspase-3 activation induced by both pro-apoptotic factors. Neuroprotective effects of NMDA on St-induced apoptosis in CGC were attenuated by inhibitors of ERK/MAPK-signaling, PD 98059 and U0126 but not by NMDA receptor antagonists, AP-5 (100 microM) and MK-801 (1 microM) or by inhibitors of PI3-K/Akt pathway (LY 294002 and wortmannin). In contrast to staurosporine model of apoptosis, AP-5 and MK-801 but not inhibitors of PI3-K/Akt and MAPK/ERK1/2 prevented the NMDA-mediated neuroprotection in LP-induced apoptosis of CGC. In separate experiments, we observed also the anti-apoptotic action of NMDA on St (0.5 microM)- and salsolinol (250 microM)-evoked cell death in human neuroblastoma SH-SY5Y cells without its influence on caspase-3 activity, induced by these pro-apoptotic factors. These data indicate that neuroprotection evoked by NMDA in CGC strongly depends on used pro-apoptotic agent and could engage NMDA channel function or be connected with the activation of pro-survival MAPK/ERK1/2 pathway. It is also suggested that anti-apoptotic effects of NMDA is connected with inhibition of fragmentation of DNA via caspase-3-independent mechanism.
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PMID:Different mechanisms of NMDA-mediated protection against neuronal apoptosis: a stimuli-dependent effect. 1946 33

Many Genista species (Leguminosae), containing isoflavones as biologically active substances, show interesting biological properties such as hypoglycemic, antiinflammatory, antiulcer, spasmolytic, antioxidant, estrogenic and cytotoxic activity against different human cancer cell lines. In this work, we describe the chemical composition of the methanolic extracts from aerial parts of Genista sessilifolia DC. and Genista tinctoria L., and their biological activity testing the effect on pBR322 DNA cleavage induced by hydroxyl radicals (*OH), generated from UV-photolysis of hydrogen peroxide (H(2)O(2)) and by nitric oxide (NO). In addition, we investigated the growth inhibitory activity of these natural products against human melanoma cell line (M14). The extracts of G. sessilifolia and G. tinctoria, for their isoflavone components, showed a protective effect on UV light and nitric oxide-mediated plasmid DNA damage, and inhibited the growth of melanoma cells. The data of the present study also suggest that these natural products could trigger apoptotic death in M14 cells. In fact, a high DNA fragmentation (COMET assay) and a significant increase of caspase-3 activity, not correlated to LDH release, a marker of membrane breakdown, occurred in melanoma cells exposed to these extracts. The significant production of reactive oxygen species (ROS) evidenced in these experimental conditions could contribute to trigger the apoptosis cascades.
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PMID:Genista sessilifolia DC. and Genista tinctoria L. inhibit UV light and nitric oxide-induced DNA damage and human melanoma cell growth. 1949 19

Bone marrow derived stromal cells (MSCs) can prevent the apoptosis of ischemic cardiomyocytes (CMCs). This anti-apoptosis activity may be related to an activation of the HIF-1alpha signal pathway in MSCs. Therefore, we investigated protective effects of an adenovirus (Ad)-mediated active form of HIF-1alpha (HIF-1alpha-Ala564-Ala803) modified MSCs on CMCs against CoCl(2)-induced apoptosis. At normoxia, pAd-HIF1alpha-Ala564-Ala803 exhibited a stable HIF-1alpha protein expression in MSCs. Compared with the single CMC culture, the TGF-beta1 level and the Bcl-2 expression were significantly increased, concomitant with a reduced expression of caspase-3, the LDH release and TUNEL-positive CMCs in CMC and MSC, beta-galactosidase (LacZ)-MSC or HIF-1alpha-Ala564-Ala803-MSC coculture exposed to CoCl(2). Furthermore, these effects were more prominent in CMC and HIF-1alpha-Ala564-Ala803-MSC coculture than in CMC and MSC or LacZ-MSC coculture exposed to CoCl(2). Pre-transfection of TGF-beta1-small interfering RNA (siRNA) effectively inhibited the TGF-beta1 level, resulting in a dramatic reduction in the Bcl-2 expression as well as an increased level of apoptosis in CMC and HIF-1alpha-Ala564-Ala803-MSC coculture exposure to CoCl(2), whereas pre-transfection of green fluorescent protein (GFP)-siRNA had no such effects. These data suggest that HIF1alpha-Ala564-Ala803 modified MSCs have better protective effects of CMCs against the CoCl(2)-induced apoptosis and these protective effects are at least partly TGF-beta1-mediated.
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PMID:Bone marrow derived stromal cells modified by adenovirus-mediated HIF-1alpha double mutant protect cardiac myocytes against CoCl2-induced apoptosis. 1952 Jan 52

The effects of cocoa feeding against N-nitrosodiethylamine (DEN)-induced liver injury were studied in rats. Animals were divided into five groups. Groups 1 and 2 were fed with standard and cocoa-diet, respectively. Groups 3 and 4 were injected with DEN at 2 and 4 weeks, and fed with standard and cocoa-diet, respectively. Group 5 was treated with DEN, received the standard diet for 4 weeks and then it was replaced by the cocoa-diet. DEN-induced hepatic damage caused a significant increase in damage markers, as well as a decrease in the hepatic glutathione, diminished levels of p-ERK and enhanced protein carbonyl content, caspase-3 activity and values of p-AKT and p-JNK. The cocoa-rich diet prevented the reduction of hepatic glutathione concentration and catalase and GPx activities in DEN-injected rats, as well as diminished protein carbonyl content, caspase-3 activity, p-AKT and p-JNK levels, and increased GST activity. However, cocoa administration did not abrogate the DEN-induced body weight loss and the increased levels of hepatic-specific enzymes and LDH. These results suggested that cocoa-rich diet attenuates the DEN-induced liver injury.
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PMID:A diet rich in cocoa attenuates N-nitrosodiethylamine-induced liver injury in rats. 1960 30

Although magnolol is cytoprotective against warm ischemia/reperfusion injury, its effect on cold preservation has not been fully investigated. This study aimed at examining whether magnolol maintains the liver graft integrity after cold preservation and elucidating the underlying mechanisms in terms of apoptotic signaling under both normothermic and hypothermic conditions. After being preserved in Ringer's lactate (RL) at 4 degrees C for 6h ex vivo, the magnolol-treated grafts demonstrated significantly higher AST, ALT, and LDH levels in perfusates than those from negative controls. TUNEL staining showed no difference in the number of apoptotic nuclei in both groups, whereas a more intense apoptotic signal in magnolol-treated grafts was shown as compared with the controls. In vitro data showed no significant difference in viability of RL-preserved clone-9 hepatocytes between the magnolol-treated and control groups, while magnolol pretreatment at 30min before cold preservation prominently induced hepatocyte cell death. RT-PCR and Western blotting analyses revealed a suppression in Bcl-2, but an up-regulation in Bax expression in clone-9 cells after magnolol treatment. Magnolol suppressed the ratios of NF-kappaB to I-kappaBalpha protein contents and I-kappaBalpha phosphorylation induced by TNF-alpha, and potentiated mitochondrial cytochrome c release and subsequent caspase-3 cleavage. Conversely, caspase-3 inhibitor attenuated magnolol-induced hepatotoxicity. We concluded that magnolol could not protect liver grafts from cold ischemia/reperfusion injury. High concentration of magnolol under serum-reduced conditions attenuates NF-kappaB-mediated signaling and induces intrinsic apoptotic pathway, thereby inducing in vitro hepatotoxicity.
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PMID:High concentration of magnolol induces hepatotoxicity under serum-reduced conditions. 1968 8

The effect of epigallocatechin-3-O-gallate (EGCG), a major component of green tea, on platelet preservation was evaluated. Single donor platelets (N = 10) were collected and preserved by the standard method. EGCG was added to the platelet concentrates before preservation and then the functional and biochemical parameters were monitored throughout the storage period. After 6 days of preservation, the aggregability of the platelets was significantly maintained by addition of 50 and 100 microg/ml of EGCG. Platelet prothrombinase activity was also significantly retained by the addition of EGCG. The accumulation of P-selectin and RANTES in the plasma preserved with EGCG was less than those preserved without EGCG, which indicated that EGCG might inhibit platelet activation. Furthermore, EGCG reduced the increase of LDH in plasma during preservation and inhibited the activation of caspase-3 and cleavage of gelsolin, thereby showing that EGCG could inhibit the apoptosis of platelets. These results suggest that EGCG may play an effective role in preserving platelets by inhibiting the activation and apoptosis of platelets.
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PMID:Preservation of platelets by adding epigallocatechin-3-o-gallate to platelet concentrates. 1977 12

Apoptosis is one of the major characteristics of delayed neuronal degeneration in neuronal injury following cerebral ischemia. Hypoxia-induced apoptosis may be co-regulated by HIF-1alpha as well as many other factors. In recent years, numerous studies concerning panaxynol (PNN) have been reported. However, whether PNN can show anti-hypoxia properties is still unknown. In this study, the protective effects of PNN on OGD-induced neuronal apoptosis and potential mechanisms were investigated. Pretreatment of the cells with PNN for 24h following exposure to OGD resulted in a significant elevation of cell survival determined by MTT assay, LDH assay, Hoechst staining and flow cytometric assessment. In addition to enhancing the expression of HIF-1alpha, PNN also normalized the caspase-3 expression/activation and increased the Bcl-2/Bax ratio. In our study, the increased level of HIF-1alpha with decreased cellular apoptosis suggested an important role for HIF-1alpha in hypoxic neurons. These results indicated that the neuroprotective effects of PNN on hypoxic neurons were at least partly due to up-regulation of HIF-1alpha and raised the possibility that PNN might reduce neurodegenerative disorders and ischemic brain diseases.
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PMID:Panaxynol protects cortical neurons from ischemia-like injury by up-regulation of HIF-1alpha expression and inhibition of apoptotic cascade. 1980 Mar 26


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