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)

This study examined the effect of Saeng-Ji-Hwang (SJH: Radix Rehmanniae) on cardiac muscle cells. Adriamycin-exposed H9C2 cardiac muscle cells were treated with a water extract of SJH. The adriamycin induced cell death and caspase-3 activation were significantly inhibited by SJH (2 mg/ml), which can be explained by the increase in Bcl-2 expression and the inhibition of Bax expression. Adriamycin reduced the Mn-SOD protein expression level in H9C2 cardiac muscle cells but a SJH treatment partially but significantly reversed this effect. Manganese (Mn)-TBAP or Mn-TMyM--mitochondria-specific SOD mimetic agent--reduced the adriamycin-induced cytotoxicity. It was also shown that SJH inhibits the release of H2O2 and prevents lipid peroxidation in the presence of adriamycin. This study examined the intracellular GSH level, which showed that adriamycin significantly decreased the intracellular GSH level but SJH increased it. BSO, a selective inhibitor of glutamyl cysteinyl ligase, which is a rate-limiting enzyme in GSH synthesis, did not affect the viability of the cardiac muscle cells. However, a combination of BSO with SJH in the presence of adriamycin reversed the SJH-induced protection. Overall, the results suggest that SJH-associated Mn-SOD and GSH are important factors in the mechanism of the SJH-induced protective mechanism in H9C2 cardiac muscle cells.
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PMID:Saeng-Ji-Hwang has a protective effect on adriamycin-induced cytotoxicity in cardiac muscle cells. 1582 71

The mechanism of how fluoride causes fluorosis remains unknown. Exposure to fluoride can inhibit protein synthesis, and this may also occur by agents that cause endoplasmic reticulum (ER) stress. When translated proteins fail to fold properly or become misfolded, ER stress response genes are induced that together comprise the unfolded protein response. Because ameloblasts are responsible for dental enamel formation, we used an ameloblast-derived cell line (LS8) to characterize specific responses to fluoride treatment. LS8 cells were growth-inhibited by as little as 1.9-3.8 ppm fluoride, whereas higher doses induced ER stress and caspase-mediated DNA fragmentation. Growth arrest and DNA damage-inducible proteins (GADD153/CHOP, GADD45alpha), binding protein (BiP/glucose-responsive protein 78 (GRP78), the non-secreted form of carbonic anhydrase VI (CA-VI), and active X-box-binding protein-1 (Xbp-1) were all induced significantly after exposure to 38 ppm fluoride. Unexpectedly, DNA fragmentation increased when GADD153 expression was inhibited by short interfering RNA treatment but remained unaffected by transient GADD153 overexpression. Analysis of control and GADD153(-/-) embryonic fibroblasts demonstrated that caspase-3 mediated the increased DNA fragmentation observed in the GADD153 null cells. We also demonstrate that mouse incisor ameloblasts are sensitive to the toxic effects of high dose fluoride in drinking water. Activated Ire1 initiates an ER stress response pathway, and mouse ameloblasts were shown to express activated Ire1. Ire1 levels appeared induced by fluoride treatment, indicating that ER stress may play a role in dental fluorosis. Low dose fluoride, such as that present in fluoridated drinking water, did not induce ER stress.
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PMID:Fluoride induces endoplasmic reticulum stress in ameloblasts responsible for dental enamel formation. 1584 62

Our group has previously shown that polyamine depletion delays apoptosis in rat intestinal epithelial (IEC-6) cells (Ray RM, Viar MJ, Yuan Q, and Johnson LR, Am J Physiol Cell Physiol 278: C480-C489, 2000). Here, we demonstrate that polyamine depletion inhibits gamma-irradiation-induced apoptosis in vitro and in vivo. Pretreatment of IEC-6 cells with 5 mM alpha-difluoromethylornithine (DFMO) for 4 days significantly reduced radiation-induced caspase-3 activity and DNA fragmentation. This protective effect was prevented by the addition of 10 muM exogenous putrescine. Radiation exposure to mice resulted in a high frequency of apoptosis over cells positioned fourth to seventh in crypt-villus units. Pretreatment of mice with 2% DFMO in drinking water significantly reduced apoptotic cells from approximately 2.75 to 1.61 per crypt-villus unit, accompanied by significant decreases in caspase-3 levels. Further examination showed that DFMO pretreatment inhibited the radiation-induced increase in the proapoptotic protein Bax. Moreover, DFMO pretreatment significantly enhanced the intestinal crypt survival rate by 2.1-fold subsequent to radiation and ameliorated mucosal structural damage. We conclude that polyamine depletion by DFMO inhibits gamma-irradiation-induced apoptosis of intestinal epithelial cells both in vitro and in vivo through inhibition of Bax and caspase-3 activity, which leads to attenuation of radiation-inflicted intestinal injury. These data indicate that DFMO may be therapeutically useful to counteract the gastrointestinal toxicity caused by chemoradiotherapy. This is the first demonstration that polyamines are required for apoptosis in vivo.
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PMID:Polyamine depletion inhibits irradiation-induced apoptosis in intestinal epithelia. 1586 Jun 39

It is known that heavy metals can accumulate in tissues during aquatic organism growth (bioaccumulation) and often biomagnify up the food chain interfering with the health and reproduction of both wildlife and humans. Recently, cadmium (Cd) was included in the endocrine disruptors list, exerting its effect on gametes quality and reproductive functions; in addition, its role as apoptotic factor was evidenced in different cell types and tissues. In the present study, the effects of two different Cd doses on testis and liver of the black goby Gobius niger were analyzed. Cd concentration in the water and its uptake by the gills were measured by differential pulse anodic stripping voltammetry. Toxic, apoptotic, and stressor Cd effects were analyzed using metallothionein (MTT), caspase 3 and heath shock protein 70 (HSP70), respectively, as bioindicators. The results of the present study suggested that, in the gills, the saturation of all specific metal sites was reached only with the highest Cd dose exposure. Either testis and liver showed an increase of MTT gene expression and protein synthesis in addition to HSP70 gene expression, related with Cd concentration in the water indicating that both tissues were affected by Cd exposure. In conclusion, the present study, not only shows the toxic effect of Cd on hepatic tissue, but also indicates its potency as apoptotic factor in the testis. This is supported by the increase of caspase 3 gene expression and the presence of its active form in testis of exposed fish.
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PMID:Effects of cadmium exposure on testis apoptosis in the marine teleost Gobius niger. 1586 69

This study examined the protective effects of Ginkgo biloba extract (GbE) on the learning and memory function in aluminum-treated rats and potential mechanisms. Wistar rats were given daily aluminum chloride 500 mg/kg, i.g, for one month, followed by continuous exposure via the drinking water containing 1600 ppm aluminum chloride for up to 5 months. The ability of spatial learning and memory was tested by Morris water maze. Aluminum administration significantly increased escape latency and searching distance, indicative of brain dysfunction. GbE treatment (50-200 mg/kg, i.g) significantly protected against aluminum-induced brain dysfunction, as evidenced by decreased escape latency and searching distance compared with the Al alone group. To examine the mechanisms of the protection, the expressions of amyloid precursor protein (APP) and caspase-3 in brain regions were examined by immunohistochemistry. GbE treatment reduced the contents of APP and caspase-3 in hippocampus of aluminum-treated rats in a dose-dependent manner. At the highest dose of GbE (200 mg/kg), the immunostain for APP and caspase-3 was returned to normal levels. In summary, this study demonstrates that GbE is effective in improving the ability of spatial learning and memory of aluminum-intoxicated rats. This protection appears to be due to a decreased expression of APP and caspase-3 in rat brain, resulting in a decrease in the production of insoluble fragments of Abeta-amyloid.
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PMID:Protective effects of Ginkgo biloba leaf extract on aluminum-induced brain dysfunction in rats. 1586 99

The volatile extract from dried pericarp of Zanthoxylum schinifolium that was obtained by simultaneous distillation with dichloromethane and water was composed of 29.9% geranyl acetate, 15.8% citronella, 15.4% sabinene and the minor volatile components included beta-myrcene, linalool, (-)-isopulegol, citronellyl acetate, 1,4-dimethyl pyrazole, alpha-terpinene, 3-methyl-6-(1-methylethyl)-2-cyclo-hexene-1-o1 and trans-geraniol. The volatile extract decreased the cell viability and induced apoptotic death in HepG2 human hepatoma cells in a concentration- and time-related manner. In addition, the volatile extract increased the production of reactive oxygen species in a dose-dependent manner. Pretreatment of the cells with Trolox, a well-known antioxidant, significantly suppressed the generation of reactive oxygen species and cell death induced by the extract. However, caspase-3 activity was not changed in the extract-treated cells, suggesting that the extract-induced apoptosis of HepG2 cells is caspase-3 independent. Furthermore, in nude mice inoculated with Huh-7 human hepatoma cells, the extract significantly inhibited tumor development. These results suggest that the volatile extract from Zanthoxylum schinifolium pericarpium is a good candidate for hepatocellular carcinoma (HCC) therapy and that reactive oxygen species are the key signaling molecules in the volatile extract-induced cell death in HepG2 cells.
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PMID:The essential oils from Zanthoxylum schinifolium pericarp induce apoptosis of HepG2 human hepatoma cells through increased production of reactive oxygen species. 1586 82

Andrographolide was extracted and purified from Andrographis panicula using hexane and water partitioning followed by ethyl acetate extraction and chromatography. It showed selective cytotoxicity to prostate cancer PC-3 cells in vitro. The morphological and biochemical changes induced by the extract in carcinoma PC-3 cell death were studied. In andrographolide-treated cells, evidence of apoptosis such as cell shrinkage and surface microvilli loss after 4-hour treatment and chromatin condensation and fragmentation in H&E-stained cells between 4 to 8 hours after treatment were observed. Under electron microscopy, membrane blebbing and apoptotic bodies formation were seen after 8-hour treatment. Using immunocytochemistry staining and cellular caspase-3 activity assay, andrographolide-treated cells showed considerable caspase-3 activation and caspase-8 in PC-3 cells at 4 and 2 hours after treatment, respectively. This suggests andrographolide-induced cell death was achieved through the apoptotic pathway, via the activation of an extrinsic caspase cascade.
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PMID:Morphological and biochemical changes of andrographolide-induced cell death in human prostatic adenocarcinoma PC-3 cells. 1587 75

The pathogenesis of reexpansion pulmonary edema is not yet fully understood. We therefore studied its mechanism in a rat model in which the left lung was collapsed by bronchial occlusion for 1 h and then reexpanded and ventilated for an additional 3 h. We then evaluated the production of reactive oxygen species in the lungs using fluorescent imaging and cerium deposition electron microscopic techniques and the incidence of apoptosis using the TdT-mediated dUTP-digoxigenin nick end labeling (TUNEL) method. We found that pulmonary reexpansion induced production of reactive oxygen species and then apoptosis, mainly in endothelial and alveolar type II epithelial cells. Endothelial cells and alveolar type I and II epithelial cells in the reexpanded lung were positive for TUNEL and cleaved caspase-3. DNA fragmentation was also observed in the reexpanded lung. In addition, wet-dry ratios obtained with reexpanded lungs were significantly higher than those obtained with control lungs, indicating increased fluid content. All of these effects were attenuated by pretreating rats with a specific xanthine oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo[1,5-a]-1,3,5-triazine-4(1H)-one. It thus appears that pulmonary reexpansion activates xanthine oxidase in both endothelial and alveolar type II epithelial cells and that the reactive oxygen species produced by the enzyme induce apoptosis among the endothelial and alveolar type I and II epithelial cells that make up the pulmonary water-air barrier, leading to reexpansion pulmonary edema.
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PMID:Pulmonary reexpansion causes xanthine oxidase-induced apoptosis in rat lung. 1587 59

The proapoptotic effect of cisplatin bile acid derivatives Bamet-R2 [cis-diamminechloro-cholylglycinate-platinum(II)] and Bamet-UD2 [cis-diammine-bisursodeoxycholate-platinum(II)], developed to treat liver and intestinal tumors, was investigated in vitro using human enterohepatic cells HepG2 (hepatoblastoma), LS 174T (colon adenocarcinoma), and its cisplatin-resistant subline LS 174T/R. Uptake by wild-type tumor cells was higher for Bamets than for cisplatin. In LS 174T/R cells, copper transporter-1 was down-regulated and multidrug resistance-associated protein-2 was up-regulated. Consequently, uptake and efflux of cisplatin, but not those of Bamets, were reduced and increased, respectively. The degree of necrosis (lactate dehydrogenase release) induced by these three drugs was small and similar in all cell types. In contrast, proapoptotic effect (caspase-3 activity and DNA fragmentation) was Bamet-UD2 > cisplatin > Bamet-R2 in HepG2 and LS 174T cells, but Bamet-UD2 > Bamet-R2 >> cisplatin in LS 174T/R cells. This effect was consistent with the ability of these compounds to form DNA-adducts (DNA-platination, changes in the DNA melting temperature, and MspI-induced restriction sequence cleavage). Oral administration of Bamet-UD2 to mice induced mild apoptosis in the small intestine (ileum > duodenum), which was not severe enough to modify its structure or function as determined by water absorption and glycocholic acid uptake by in situ perfused ileum. These results indicate that Bamet-UD2 overcomes the resistance to cisplatin when this is due in part to enhanced ability of intestinal tumors to reduce intracellular cisplatin contents. Moreover, its strong proapoptotic versus its weak pronecrotic effect together with its mild effect on normal tissues, including intestinal mucosa, may account for the high antitumor activity of Bamet-UD2 together with its very low toxicity.
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PMID:Proapoptotic effect on normal and tumor intestinal cells of cytostatic drugs with enterohepatic organotropism. 1598 17

The possible antiproliferative and apoptotic inducing potentials of fresh juice prepared from Scutellaria barbata (SBJ) and warmed water extract of Radix Sophorae Tonkinensis (RSTE) have been tested on a series of cancer cell lines, including HepG2 hepatoblastoma, Hep3B hepatocellular carcinoma, MDA-MB231 breast carcinoma, A549 lung cancer and KG-1 acute myelogenous leukaemia in vitro. Both SBJ and RSTE were able to inhibit the growth of cancer cell lines and induce apoptosis. Further analysis of the action of RSTE on HepG2 cells suggested that the activity of the central machinery of apoptosis, caspase 3, was significantly elevated. Oligo-nucleosomal length DNA fragments formation was readily detected by TdT-mediated dUTP nick end labelling assay after RSTE treatment. Taken together, we believe that, although Radix Sophorae Tonkinensis was demonstrated to have toxic components including matrine and oxymatrine, it is still worthwhile to further investigate its anti-cancer potential under a safety toxicological precaution.
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PMID:Activities of fresh juice of Scutellaria barbata and warmed water extract of Radix Sophorae Tonkinensis on anti-proliferation and apoptosis of human cancer cell lines. 1601 72


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