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)

Our previous study demonstrates that SYB produces a neuroprotective effect in vivo. In the present study, we investigated the protective effect of safflor yellow B (SYB) on the acute oxidative injury induced by H(2)O(2) and mechanisms in PC12 cells. H(2)O(2) was used to mimic in vitro model of the oxidative injury and to induce apoptosis in PC12 cells. The cells were pretreated with the different concentrations of SYB. The cell viability, lactate dehydrogenase (LDH) release, malondialdehyde (MDA), and superoxide anion levels, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were measured. Caspase 3 activity, Bcl-2 and Bax expressions were also observed. The results showed that exposure of the cells to H(2)O(2) significantly decreased the cell viability, SOD and GSH-Px activities and Bcl-2 expression, and increased LDH release, superoxide anion and MDA generations, caspase 3 activity and Bax expressions. Pretreatment of the cells with SYB was able to remarkably antagonize the H(2)O(2)-induced changes in dose-dependent way. These suggest that SYB is able to protect PC12 cells from H(2)O(2)-induced injury and apoptosis via antioxidant and anti-apoptotic mechanisms.
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PMID:Safflor yellow B suppresses pheochromocytoma cell (PC12) injury induced by oxidative stress via antioxidant system and Bcl-2 /Bax pathway. 1942 80

Pentachlorophenol (PCP) (C(6)HCl(5)O) is a synthetic toxic organochloride fungicide for humans which exhibit neurotoxic properties. In the present research, we describe the potential pathways implicated in PCP-induced apoptosis in an acute model of toxicity in rat cerebellar granule neurons (CGNs). In our experiments, acute exposure of CGNs to micromolar concentrations of PCP induced the transcriptional activity of genes related to the classical apoptosis pathway (caspase 3, caspase 8, Bad), oxidative stress and glutathione metabolism (glutathione peroxidase-1, catalase, glutathione-S-transferase-3 and superoxide dismutase-1), and mitogenic response (cyclin D1, cdk2, cdk4, cdkn2b). Results from Western blot also shown significative increases in the expression of cyclins D1, E and A and cdk4. The mitogenic response was also related to a significative increase in the phosphorylation of retinoblastoma protein (Rb). PCP would cause apoptosis up-regulating the transcriptional activity of p53 gene and also increasing their activation by phosphorylation, concomitant with a decrease in the sirtuin 1 content. In conclusion, acute exposure of CGNs to PCP induces the classical p53 apoptotic pathway, promotes the up-regulation of several genes related to oxidative stress and the over-expression of molecules involved in the cell cycle control.
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PMID:Evaluation of pathways involved in pentachlorophenol-induced apoptosis in rat neurons. 1944 31

This study has evaluated the ability of the semiessential amino acid taurine to attenuate lipopolysaccharide (LPS)-induced lung inflammation, oxidative stress and apoptosis in a small animal model. For this purpose, bacterial LPS (0.02mg in phosphate buffered saline (PBS) pH 7.4) was instilled intratracheally into female Golden Syrian hamsters, before or after a 3-day intraperitoneal treatment with a single dose (50mg/kg in PBS pH 7.4) of taurine. At 24h after the last treatment, lung tissue and bronchoalveolar lavage fluid (BALF) samples were collected. In comparison to samples from animals receiving only PBS pH 7.4, serving as controls, those of LPS-stimulated animals exhibited a higher count of both total leukocytes and neutrophils in the BALF, and increased incidence of apoptosis, depletion of intracellular glutathione and evidence of inflammation confined to the parenchyma in the lung. In addition, LPS caused cells in the BALF to exhibit a higher expression of tumor necrosis factor-1, a higher activity of caspase-3, marked lipid peroxidation, and altered activities of catalase, glutathione peroxidase and superoxide dismutase relative to control samples. In contrast, a treatment with taurine was found to significantly attenuate all of the cellular and biochemical alterations induced by LPS, more so when given before rather than after the endotoxin. The present results suggest that taurine possesses intrinsic antiinflammatory and antioxidant properties that may be of benefit against the deleterious actions of LPS in the lung.
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PMID:Attenuating effect of taurine on lipopolysaccharide-induced acute lung injury in hamsters. 1946 29

Acute exercise in mice induces intestinal lymphocyte (IL) apoptosis. Freewheel running reduces apoptosis and forced exercise training increases splenocyte antioxidant levels. The purpose of this study was to examine the effect of freewheel running and acute exercise on mouse IL numbers and concentrations of apoptosis and antioxidant proteins and pro-inflammatory cytokines in IL. Female C57BL/6 mice had access to in-cage running wheels (RW) or cages without wheels (NRW) for 16 weeks and were randomized at the end of training to no exercise control (TC) or to treadmill exercise with sacrifice after 90 min of running (TREAD; 30 min, 22 m min(-1); 30 min, 25 m min(-1); 30 min, 28 m min(-1); 2 degrees slope). IL were analyzed for pro-(caspase 3 and 7) and anti-(Bcl-2) apoptotic proteins, endogenous antioxidants (glutathione peroxidase: GPx; catalase: CAT) and the pro-inflammatory cytokine, TNF-alpha. RW mice had higher cytochrome oxidase (p<0.001) and citrate synthase (p<0.01) activities in plantaris and soleus muscles and higher GPx and CAT expression in IL (p<0.05) (indicative of training) compared with NRW mice. TNF-alpha expression was lower (p<0.05) and IL numbers higher (p<0.05) in RW vs. NRW mice. No training effect was observed for apoptotic protein expression, although TREAD resulted in higher caspase and lower Bcl-2. These results suggest that freewheel running in mice for 16 weeks enhances antioxidant and reduces TNF-alpha expression in IL but does not reduce pro-apoptotic protein expression after acute exercise. Results are discussed in terms of implications for inflammatory bowel diseases where apoptotic proteins and TNF-alpha levels are elevated.
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PMID:Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-alpha in intestinal lymphocytes. 1948 47

Recent global events have focused attention on the potential threat of international and domestic chemical terrorism, as well as the possibility of chemical warfare proliferation. Sulphur mustard (SM) is one of the potent chemical warfare agents (CWA), which initiates a cascade of events that converge on the redox mechanisms common to brain injury. The present study was designed to examine the effects of chronic SM exposure on neurobehavioral impairments, mitochondrial oxidative stress in male Swiss Albino mice and its role in inducing apoptotic neuronal cell death. The animals were divided into four groups (control, low, medium and high dose) of 5 animals each. Exposure to SM was given percutaneously daily for 12 weeks. The results demonstrated impairment in neurobehavioral indices viz. rota rod, passive avoidance and water maze tests in a dose dependent manner. There was a significant increase in lipid peroxidation and protein carbonyl content whereas, decrease in the activity of manganese superoxide dismutase (MnSOD), glutathione reductase and glutathione peroxidase suggesting impaired antioxidant defense system. Immunoblotting of cytochrome c, Bcl-2, Bax and activation of caspase-3 suggest induction of apoptosis in a dose dependent manner. Finally, increased p53 expression suggests that it may target the mitochondrial pathway for inducing apoptosis in response to DNA damage signals. In conclusion, chronic SM exposure may have the potential to generate oxidative stress which may trigger the release of cytochrome c as well as caspase-3 activation in neurons leading to cell death by apoptosis in a dose dependent manner which may in the end be responsible for the disruption of cognitive functions in mice.
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PMID:Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain. 1956 Apr 81

Pyrrolizidine alkaloid (PA) clivorine, isolated from traditional Chinese medicinal plant Ligularia hodgsonii Hook, has been shown to induce apoptosis in hepatocytes via mitochondrial-mediated apoptotic pathway in our previous research. The present study was designed to observe the protection of N-acetyl-cysteine (NAC) on clivorine-induced hepatocytes apoptosis. Our results showed that 5 mM NAC significantly reversed clivorine-induced cytotoxicity via MTT and Trypan Blue staining assay. DNA apoptotic fragmentation analysis and Western-blot results showed that NAC decreased clivorine-induced apoptotic DNA ladder and caspase-3 activation. Further results showed that NAC inhibited clivorine-induced Bcl-xL decrease, mitochondrial cytochrome c release and caspase-9 activation. Intracellular glutathione (GSH) is an important ubiquitous redox-active reducing sulfhydryl (--SH) tripeptide, and our results showed that clivorine (50 microM) decreased cellular GSH amounts and the ratio of GSH/GSSG in the time-dependent manner, while 5 mM NAC obviously reversed this depletion. Further results showed that GSH synthesis inhibitor BSO augmented clivorine-induced cytotoxicity, while exogenous GSH reversed its cytotoxicity on hepatocytes. Clivorine (50 microM) significantly induced cellular reactive oxygen species (ROS) generation. Further results showed that 50 microM Clivorine decreased glutathione peroxidase (GPx) activity and increased glutathione S transferase (GST) activity, which are both GSH-related antioxidant enzymes. Thioredoxin-1 (Trx) is also a ubiquitous redox-active reducing (--SH) protein, and clivorine (50 microM) decreased cellular expression of Trx in a time-dependent manner, while 5 mM NAC reversed this decrease. Taken together, our results demonstrate that the protection of NAC is major via maintaining cellular reduced environment and thus prevents clivorine-induced mitochondrial-mediated hepatocytes apoptosis.
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PMID:Protective mechanisms of N-acetyl-cysteine against pyrrolizidine alkaloid clivorine-induced hepatotoxicity. 1962 61

Selenium is an essential micronutrient to freshwater fish, but can be very toxic at slightly above the threshold level. The liver is known to be the major site of selenium accumulation and metabolism in fish. Recent evidence from mammalian systems suggests that oxidative damage is an important mechanism of selenium toxicity; however this phenomenon has not been investigated in-depth in fish, either in vivo or in vitro. Therefore, the present study was designed to investigate whether selenium (as selenite) exposure causes cytotoxicity in fish by inducing oxidative stress. We used isolated hepatocytes in primary culture from freshwater rainbow trout (Oncorhynchus mykiss) as the model in vitro experimental system. The 24h LD(50) of selenite to trout hepatocytes was found to be 587 microM. In order to evaluate the dose-dependent response patterns of various oxidative stress parameters, the trout hepatocytes were exposed to three different doses of selenite [50, 100 and 200 microM (corresponding to approximately 10%, 20% and 35% of 24h LD(50))] in addition to control (0 microM of selenite) for 24h. We observed an induction of catalase (CAT) and superoxide dismutase (SOD) activities at 50 and 100 microM of selenite exposure, but not at 200 microM, relative to the control. In contrast, the induction of glutathione peroxidase (GPx) activity was recorded at 100 and 200 microM exposure doses, but not at 50 microM. We also demonstrated that selenite exposure (100-200 microM) increased intracellular ROS formation at an early stage (2h). The reduced to oxidized glutathione ratio (GSH:GSSG) decreased sharply with increasing selenite dose, indicating the loss of cellular reducing capacity. The cellular lipid peroxidation tended to increase with increasing selenite exposure dose, indicating the occurrence of membrane damage. A 20-40% decrease in cell viability was observed at 100 and 200 microM of selenite exposure. The increase in cell death was associated with a significant increase of caspase-3/7 activity, suggesting the induction of apoptosis. Overall, the present study suggests that selenite exposure at high level causes oxidative damage to trout hepatocytes, probably by inducing the imbalance of intracellular glutathione (GSH) redox.
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PMID:Selenite causes cytotoxicity in rainbow trout (Oncorhynchus mykiss) hepatocytes by inducing oxidative stress. 1965 Dec 3

The thioredoxin system, composed of thioredoxin reductase (TrxR), thioredoxin (Trx), and NADPH (nicotinamide adenine dinucleotide phosphate), plays a central role in regulating cellular redox homeostasis and signaling pathways. TrxR, overexpressed in many tumor cells and contributing to drug resistance, has emerged as a new target for anticancer drugs. Gold complexes have been validated as potent TrxR inhibitors in vitro in the nanomolar range. In order to obtain potent and selective TrxR inhibitors, we have synthesized a series of linear, 'auranofin-like' gold(I) complexes all containing the [Au(PEt(3))](+) synthon and the ligands: Cl(-), Br(-), cyanate, thiocyanate, ethylxanthate, diethyldithiocarbamate and thiourea. Phosphine gold(I) complexes efficiently inhibited cytosolic and mitochondrial TrxR at concentrations that did not affect the two related oxidoreductases glutathione reductase (GR) and glutathione peroxidase (GPx). The inhibitory effect of the redox proteins was also observed intracellularly in cancer cells pretreated with gold(I) complexes. Gold(I) compounds were found to induce antiproliferative effects towards several human cancer cells some of which endowed with cisplatin or multidrug resistance. In addition, they were able to activate caspase-3 and induce apoptosis observed as nucleosome formation and sub-G1 cell accumulation. The complexes with thiocyanate and xanthate ligands were particularly effective in inhibiting thioredoxin reductase and inducing apoptosis. Pharmacodynamic studies in human ovarian cancer cells allowed for the correlation of intracellular drug accumulation with TrxR inhibition that leads to the induction of apoptosis via the mitochondrial pathway.
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PMID:Cancer cell death induced by phosphine gold(I) compounds targeting thioredoxin reductase. 1966 52

To investigate the antioxidative effects of ginsenosides [protopanaxadiol derivatives (PD):protopanaxatriol derivatives (PT) = 1:1] from the roots of Korean ginseng, cell viability, malondialdehyde (MDA) production, antioxidant enzyme activities, and expressions of apoptosis were analyzed after pretreatment of human hepatoma HepG2 cells with H(2)O(2). Cell death was increased through H(2)O(2) treatment dose dependently, and a dose of ginseng extract (PD:PT = 1:1) of 18.6 microg/mL was enough to derive it in reverse. MDA production was reduced through the administration of ginseng extracts even with more intensive H(2)O(2) treatments. Through the use of even low levels of ginseng extract (e.g., 1.86 microg/mL), catalase (CAT) activity was easily reduced from the plateau induced by H(2)O(2). The glutathione peroxidase activity was no better than that of CAT. We assume that ginseng extract acts as an antioxidant even when effective levels of ginseng differ. A ginseng extract dose of 18.6 microg/mL increased the apoptotic expression of oxidative stressed signals, such as c-Jun-N-terminal kinase and stress-activated protein kinase expressions, and mitochondrial cytochrome c released caspase-3 activation; however, these expressions changed with higher doses of ginseng.
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PMID:Antioxidant and apoptotic effects of korean white ginseng extracted with the same ratio of protopanaxadiol and protopanaxatriol saponins in human hepatoma HepG2 cells. 1972 59

Alzheimer's disease is the most common form of dementia. Amyloid-beta protein is considered as a key factor of pathogenesis of Alzheimer's disease. l-3-n-butylphthalide (L-NBP), an anti-cerebral ischemia drug, has been shown to have therapeutic effects in vascular dementia animal models. In the present study, we investigated the potential of L-NBP to protect against cognitive impairment, oxidative damage and neuropathological changes induced by intracerebroventricular infusion of amyloid-beta peptide in rats. Daily treatments of 10 and 30 mg/kg L-NBP significantly improved spatial learning deficits and attenuated working memory deficits in Morris water maze task. L-NBP partially reversed the reduction of glutathione peroxidase activities and decreased malondialdehyde levels in the cortex and hippocampus. Furthermore, L-NBP markedly inhibited amyloid-beta-induced neuronal apoptosis, possibly by blocking caspase-3 activation. In addition, L-NBP reduced activation of glycogen synthase kinase-3beta and tau protein phosphorylation. Our results demonstrate that L-NBP protects against amyloid-beta-induced neurodegeneration and cognitive decline in a rat model, suggesting that it may have potential as a therapy for Alzheimer's disease.
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PMID:L-3-n-butylphthalide improves cognitive impairment induced by intracerebroventricular infusion of amyloid-beta peptide in rats. 1973 53


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