Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The anti-proliferative activity of hesperetin, hesperidin, neohesperidin and rutin was evaluated on human hepatoma cell lines (Hep G2) and correlated to their antioxidant activity. The results obtained showed strong anti-proliferative effects of hesperidin and neohesperidin, considerably higher than the other two additives. Hesperetin induced caspase-3 activation, release of LDH and endogenous accumulation of putrescine. Cell cycle distribution seems to indicate that the inhibitory effects of polyphenols on cell growth could be due to G0/G1 block, and activation of apoptotic pathway in the presence of hesperetin. Our results underline also that the glycone forms show reduced scavenging activity against DPPH, but present a remarkable inhibition of cell proliferation and low cytotoxicity.
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PMID:Influence of L-rhamnosyl-D-glucosyl derivatives on properties and biological interaction of flavonoids. 1898 44

Fumonisins are mycotoxins produced by Fusarium verticillioides. The toxic effects of fumonisin B(1) (FB(1)) at the cellular level consist of a mixture of both necrosis and apoptosis. We studied the effect of FB(1) in human lung fibroblasts (NHLF) and human kidney epithelial cells (RPTEC) in primary culture. Apoptotic and necrotic cell death, collagen and fibronectin secretion were determined mainly after 14 days' exposure. The protein content of NHLF and RPTEC cells was slightly increased after 14 days' exposure to low FB(1) concentrations (0.1 or 1 microm). Caspase-3 activity tended to increase in NHLF and to decrease in RPTEC cells with higher FB(1) concentrations after 14 days' exposure. LDH release was slightly decreased in both cell types after 14 days. Collagen I and III secretion was enhanced in NHLF cells. Collagen III was decreased in RPTEC. Collagen IV was not changed in both cell types. Fibronectin secretion was uninfluenced in RPTEC and interim increased in NHLF. Furthermore LC-MS/MS studies did not give any hints for a metabolism of FB(1). Therefore, the main risk of prolonged FB(1) exposure seems to be altered collagen secretion pattern.
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PMID:Effects of the mycotoxin fumonisin B(1) on cell death in human kidney cells and human lung fibroblasts in primary culture. 1898 66

It was found previously that organophosphorus pesticides (OPs) significantly inhibited cytotoxic T lymphocyte (CTL) activity. To explore the mechanism of OP-induced inhibition of CTL activity, the present study investigated whether OPs can induce cell death/apoptosis in T cells. Jurkat human T cells were treated with chlorpyrifos at 0-100 ppm for 2, 4, and 6h at 37 degrees C in vitro. It was found that chlorpyrifos induced cell death of Jurkat human T cells in a dose- and time-dependent manner, as shown by MTT and LDH assays. Then, it was investigated if chlorpyrifos-induced cell death consisted of apoptosis, as determined by analysis of Annexin-V staining and the intracellular level of active caspase-3 by flow cytometry, and DNA fragmentation analysis. It was found that chlorpyrifos induces apoptosis in Jurkat T cells in a dose- and time-dependent manner, as determined by analysis of Annexin-V staining. DNA fragmentation was detected when cells were treated with 50 or 100 ppm chlorpyrifos for 4 and 6h. Chlorpyrifos also induced an increase in intracellular active caspase-3 in Jurkat T cells in a dose- and time-dependent manner, and a caspase-3 inhibitor, Z-DEVD-FMK, significantly inhibited chlorpyrifos-induced apoptosis. These findings indicate that chlorpyrifos can induce apoptosis in human Jurkat T cell cells, and this effect is partially mediated by the activation of intracellular caspase-3.
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PMID:Chlorpyrifos induces apoptosis in human T cells. 1899 66

We investigated the effects of a novel Na(+)/H(+) exchanger-1 (NHE-1) inhibitor KR-33028 on glutamate excitotoxicity in cultured neuron cells in vitro and cerebral infarct in vivo by comparing its potency with that of zoniporide, a well-known, highly potent NHE-1 inhibitor. KR-33028 inhibited NHE-1 activation in a concentration-dependent manner (IC(50)=2.2 nM), with 18-fold greater potency than that of zoniporide (IC(50)=40.7 nM). KR-33028 significantly attenuated glutamate-induced LDH release with approximately 100 times lower EC(25) than that of zoniporide in cortical neurons in vitro (EC(25) of 0.007 and 0.81 microM, respectively), suggesting its 100-fold greater potency than zoniporide in producing anti-necrotic effect. In addition, the EC(50) of KR-33028 for anti-apoptotic effect was 100 times lower than that of zoniporide shown by TUNEL positivity (0.005 and 0.62 microM, respectively) and caspase-3 activity (0.01 and 2.64 microM, respectively). Furthermore, the EC(50) value of KR-33028 against glutamate-induced intracellular Ca(2+) overload was also 100 times lower than that of zoniporide (EC(50) of 0.004 and 0.65 microM, respectively). In the in vivo cerebral infarct model (60 min middle cerebral artery occlusion followed by 24 h reperfusion), KR-33028 reduced infarct size in a dose-dependent manner. Its ED(25) value, however, was quite similar to that of zoniporide (ED(25) of 0.072 and 0.097 mg/kg, respectively). Hence these results suggest that the novel NHE-1 inhibitor, KR-33028, could be an efficient therapeutic tool to protect neuronal cells against ischemic injury.
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PMID:Effects of KR-33028, a novel Na+/H+ exchanger-1 inhibitor, on glutamate-induced neuronal cell death and ischemia-induced cerebral infarct. 1902 30

Ochratoxin A (OTA) is a mycotoxin produced by several fungi growing on food source material. The main target of OTA is the kidney. So far, mainly cell lines of different origin have been used to study OTA toxicity. Yet all of them derived from tubule segments and therefore only limited information is available on glomerular effects of OTA. We exposed human mesangial cells in primary culture to OTA in nanomolar concentrations for up to 14 days. Necrotic and apoptotic cell death as well as fibrotic changes were studied. Protein content decreased only when unusual high OTA concentrations were used (1 microM). By contrast, an increase of caspase-3 activity or LDH release was observed after five days already at 10 nM OTA. A decrease of collagen I secretion was accompanied by a virtually unchanged collagen III and fibronectin secretion. Collagen IV secretion was slightly increased at low OTA concentrations (0.3-10 nM). We conclude that OTA has only a minor effect on human mesangial cells in primary culture. OTA did not influence collagen homeostasis substantially. Based on the data presented here, a risk of mesangial damage by OTA exposure is unlikely.
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PMID:Effect of ochratoxin A on cell survival and collagen homeostasis in human mesangial cells in primary culture. 1903 72

Although it has long been recognized that thyroid hormone is an effective positive inotrope, its efficacy in supporting hemodynamics in the acute setting of ischaemia and reperfusion (R) without worsening reperfusion injury remains largely unknown. Thus, we investigated the effects of triiodothyronine (T3) on reperfusion injury in a Langendorff-perfused rat heart model of 30 min zero-flow ischaemia and 60 min of (R) with or without T3 (40 microg/l) at R, T3-R60, n = 11 and CNT-R60, n = 10, respectively. Furthermore, phosphorylated levels of intracellular kinases were measured at 5, 15 and 60 min of R. T3 markedly improved postischaemic recovery of left ventricular developed pressure (LVDP%); 56.0% (SEM, 4.4) in T3-R60 versus 38.8% (3.1) in CNT-R60, P < 0.05. Furthermore, LDH release was significantly lower in T3-R60. Apoptosis detection by fluorescent probe optical imaging showed increased fluorescent signal in CNT-R60 hearts, while the signal was hardly detectable in T3-R60 hearts. Similarly, caspase-3 activity was found to be 78.2 (8.2) in CNT-R60 vs 40.5 (7.1) in T3-R60 hearts, P < 0.05. This response was associated with significantly lower levels of phospho-p38 MAPK at any time point of R. No significant changes in phospho- ERK1/2 and JNK levels were observed between groups. Phospho-Akt levels were significantly lower in T3 treated group at 5 min and no change in phospho-Akt levels were observed at 15 and 60 min between groups. In conclusion, T3 administration at reperfusion can improve postischaemic recovery of function while limiting apoptosis. This may constitute a paradigm of a positive inotropic agent with anti-apoptotic action suitable for supporting hemodynamics in the clinical setting of ischaemia-reperfusion.
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PMID:Thyroid hormone improves postischaemic recovery of function while limiting apoptosis: a new therapeutic approach to support hemodynamics in the setting of ischaemia-reperfusion? 1910 50

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


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