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

The neuroprotective effects of oestrogens have been demonstrated against a variety of insults, including excitotoxicity, oxidative stress and cerebral ischemia under certain conditions. However, the molecular mechanisms underlying oestrogen neuroprotection are still unclear. We aimed to determine whether 17beta-oestradiol (E(2)) administration post-hypoxia (p-hx) was neuroprotective and whether these actions were mediated through oestrogen receptors (ER). For this purpose, 12-embyonic day-old chickens were subjected to acute hypoxia [8% (O(2)), 60 min], followed by different reoxygenation periods. To test the neuroprotective effect of E(2) and its mechanism, embryos were injected 30 min after the end of hypoxia with E(2) alone or with ICI 182 780, a competitive antagonist of ER. Cytochrome c (cyt c) release, an indicator of mitochondrial apoptotic pathway, was measured by western blot in optic lobe cytosolic extracts. DNA fragmentation by TUNEL fluorescence and caspase-3 fragmentation by immunofluorescence were detected on optic lobe sections. Acute hypoxia produces a significant increase in cyt c release from mitochondria at 4 h p-hx, followed by an increase in TUNEL positive cells 2 h later (6 h p-hx). Administration of E(2) (0.5 mg/egg) produced a significant decrease in cytosolic cyt c levels at 4 h p-hx, in caspase-3 activation and in TUNEL positive cells at 6 h p-hx compared to vehicle treated embryos. In the E(2)-ICI 182 780 treated embryos, cyt c release, caspase-3 fragmentation and TUNEL positive cells were similar to the hypoxic embryos, thus suggesting the requirement of an E(2)-ER interaction for E(2) mediated neuroprotective effects. In conclusion, E(2) prevents hypoxia-induced cyt c release and posterior cell death and these effects are mediated by oestrogen receptors.
 ...
PMID:Hypoxia-induced apoptotic cell death is prevented by oestradiol via oestrogen receptors in the developing central nervous system. 1820 55

The cell death cascades in different brain regions namely hippocampus and frontal cortex of rats fed with 10% (v/v) ethanol for 12 weeks, was examined. After Western blotting, different cell death associated proteins displayed differential activation in the two regions observed. In hippocampus, activated caspase-3 and caspase-7 resulted in subsequent cleavage of poly(ADP-ribose) polymerase-1 (PARP-1). Cytochrome c release to cytosol and apoptosis inducing factor (AIF) translocation to nucleus was marginal. B-cell leukemia/lymphoma-2 (Bcl-2) translocation to cytosol was significant whereas Bcl-2-associated X protein (Bax) and Bcl-associated death protein (Bad) were largely located in cytosol. Further, upregulation of N-methyl D-aspartate receptor subunit 1 (NMDAR1), N-methyl D-aspartate receptor subunit 2B (NMDAR2B), N-methyl D-aspartate receptor subunit 2C (NMDAR2C) and activation of calpains were observed. In frontal cortex, caspase-3 activation, cleavage of PARP-1 and nuclear translocation of AIF were more pronounced. Moreover, cytochrome c release to cytosol, Bcl-2 translocation to cytosol was evident. However, levels of Bax, Bad, NMDA receptor subunits, and calpains were unaffected. Apoptosis was further substantiated by in situ staining for terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL). Results of the current study revealed that frontal cortex exhibits a higher level of ethanol-induced apoptosis relative to hippocampus. DNA polymerase beta assay and immunoblot showed significant loss in base excision repair in ethanol treated group.
 ...
PMID:Cell death is associated with reduced base excision repair during chronic alcohol administration in adult rat brain. 1825 62

ST13 is a cofactor of heat shock protein 70 (Hsp70). To date, all data since the discovery of ST13 in 1993 until more recent studies in 2007 have proved that ST13 is downregulated in tumors and it was proposed to be a tumor suppressor gene, but no work reported its antitumor effect and apoptotic mechanism. In the work described in this paper, ST13 was inserted into ZD55, an oncolytic adenovirus with the E1B 55-kDa gene deleted, to form ZD55-ST13, which exerts an excellent antitumor effect in vitro and in an animal model of colorectal carcinoma SW620 xenograft. ZD55-ST13 inhibited tumor cells 100-fold more than Ad-ST13 and ZD55-EGFP in vitro. However, ZD55-ST13 showed no damage of normal fibroblast MRC5 cells. In exploring the mechanism of ZD55-ST13 in tumor cell killing, we found that ZD55-ST13-infected SW620 cells formed apoptotic bodies and presented obvious apoptosis phenomena. ZD55-ST13 induced the upregulation of Hsp70, the downregulation of antiapoptotic gene Bcl-2, and the release of cytochrome c. Cytochrome c triggered apoptosis by activating caspase-9 and caspase-3, which cleave the enzyme poly(ADP-ribose) polymerase in ZD55-ST13-infected SW620 cells. In summary, overexpressed ST13 as mediated by oncolytic adenovirus could exert potent antitumor activity via the intrinsic apoptotic pathway and has the potential to become a novel therapeutic for colorectal cancer gene therapy.
 ...
PMID:Potent antitumor efficacy of ST13 for colorectal cancer mediated by oncolytic adenovirus via mitochondrial apoptotic cell death. 1835 16

Pseudomonas aeruginosa is a gram-negative opportunistic pathogen that is cytotoxic towards a variety of eukaryotic cells. To investigate the effect of this bacterium on monocyte, we infected human U937 cells with the P. aeruginosa strain in vitro. To explore the expression of Bcl-2 and Bax as well as caspase-3/9 activation in the apoptosis of human U937 cells induced by P. aeruginosa, Hoechst 33258 staining and Giemsa staining as well as Flow cytometry analysis were used to determine the rate of apoptosis, and the expressions of Bcl-2 and Bax were assayed by RT-PCR and Western blotting respectively. Bax protein conformation change was assayed by immunoprecipitation. Cytochrome c release was measured by Western blotting. Moreover, exposure of U937 cells to P. aeruginosa measured caspase-3/9 activity. It was found that the apoptosis of human U937 cells could be induced by Pseudomonas aeruginosa in a dose- and time-dependent manner. Also, there were a tendency of alterations with an increased expression level of Bax and a reduced expression level of Bcl-2, increased levels of cytochrome c release, and also with an increased activation of caspase-3/9 and Bax protein conformation change. For the evaluation of the role of caspases, caspase-3/9 inhibitors Z-DEVD-FMK and Z-LEHD-FMK respectively were used. The results were further confirmed by the observation that the caspase inhibitors Z-DEVD-FMK and Z-LEHD-FMK blocked P. aeruginosa-induced U937 apoptosis. It is concluded that P. aeruginosa can induce apoptosis with an up-regulated expression of Bax and a down-regulated expression of Bcl-2, which resulted in increased levels of cytochrome c release and increased caspase-3 and -9 in human U937 cells.
 ...
PMID:Role of Bcl-2 family members in caspase-3/9-dependent apoptosis during Pseudomonas aeruginosa infection in U937 cells. 1841 81

In the human colon cancer cells HCT116, deoxycholic acid (DCA) induces apoptosis via the mitochondrial pathway by triggering the release of mitochondrial factors such as cytochrome c. To elucidate if Bax, a proapoptotic member of the Bcl-2 family known to trigger cytochrome c release in response to various types of apoptotic stimuli, is involved in DCA-induced apoptosis in HCT116 cells, we analyzed DCA-induced apoptosis in Bax-knockout (Bax(-/-)) HCT116 cells. Cytochrome c release and caspase-9 activation were detectable after 5 min in both Bax(-/-) and Bax(+/-) HCT116 cells. Caspase-3 and caspase-8 activation was observed after 15 and 30 min, respectively. Bax(-/-) cells were protected from apoptosis by treating them with ursodeoxycholic acid for 12 h prior to DCA treatment. These results are consistent with our previous observations that were obtained by using wild-type HCT116 cells and suggest that Bax is not indispensable for DCA-induced apoptosis in HCT116 cells.
 ...
PMID:Deoxycholic acid can induce apoptosis in the human colon cancer cell line HCT116 in the absence of Bax. 1844 40

Free radicals induce oxidative stress in vivo, leading to various disorders and diseases. In the present study, the effect of oxygen pressure on the cytotoxicity induced by free radicals was studied. It was found that alkyl radicals markedly aggravated Jurkat cell apoptosis under low oxygen pressure and this was ascribed to a hypoxic condition caused by the consumption of oxygen by alkyl radicals giving peroxyl radicals and subsequent lipid peroxidation by a chain mechanism. The intracellular lipid hydroperoxides significantly increased at an early time point even under hypoxia. Cytochrome c was released from the mitochondria, and caspase-9 as well as caspase-3 was activated during apoptosis, indicating that cell death followed by the intrinsic, mitochondrial apoptosis pathway. Pretreatment with VAD-FMK, a caspase inhibitor, attenuated the apoptosis induced by alkyl radicals under hypoxia. Moreover, pretreatment with various antioxidants also significantly rescued the cells from apoptosis. Taken together, the results indicate that free radicals induced hypoxic conditions, which accelerated mitochondria-dependent cell apoptosis.
 ...
PMID:Effect of oxygen concentration on free radical-induced cytotoxicity. 1854 Jan 11

Defects in mitochondrial function have been shown to participate in the induction of neuronal cell injury. The present study assessed the preventive effect of a prostaglandin E(1) analogue misoprostol against the toxicity of parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) with respect to the mitochondria-mediated cell death process and oxidative stress. MPP(+) induced the nuclear damage, the changes in the mitochondrial membrane permeability, the formation of reactive oxygen species and the depletion of GSH, which leads to cell death in differentiated PC12 cells. Misoprostol prevented the toxic effect of MPP(+). Treatment with misoprostol significantly attenuated the MPP(+)-induced mitochondrial membrane permeability change that leads to the increase in pro-apoptotic Bax and Cytochrome c levels, and subsequent caspase-3 activation. The protective effect of misoprostol may be supported by the inhibitory effect of prostaglandin E(1) on the MPP(+) toxicity. Misoprostol significantly attenuated another parkinsonian neurotoxin rotenone-induced cell death. The results show that misoprostol may prevent the MPP(+) toxicity by suppressing the mitochondrial membrane permeability change that leads to the Cytochrome c release and caspase-3 activation. The preventive effect seems to be ascribed to the inhibitory effect on the formation of reactive oxygen species and depletion of GSH.
 ...
PMID:Prostaglandin analogue misoprostol attenuates neurotoxin 1-methyl-4-phenylpyridinium-induced mitochondrial damage and cell death in differentiated PC12 cells. 1860 72

To elucidate the mechanism by which L-carnitine and related metabolites inhibited mitochondria-dependent apoptosis, we used conditional TRX2-knockout DT40 cells (TRX2(-/-)) and compared the properties of signaling pathways leading to apoptosis in the wild and TRX2(-/-) cells. Caspase-3 and 9, but not caspase-8, were strongly activated in TRX2(-/-) cells but not in wild cells. TRX2(-/-) cells generated large amounts of reactive oxygen species that markedly decreased cellular glutathione levels both in cytosol and mitochondria. We found that the critical thiol groups of adenine nucleotide translocator (ANT) were oxidized more easily in TRX2(-/-) cells than in wild cells and that the reduced form, but not oxidized form, of ANT selectively bound to TRX2. Cytochrome c and SOD1 were released from mitochondria more easily in TRX2(-/-) cells than in wild cells. All these phenomena observed with TRX2(-/-) cells were effectively inhibited by acetyl-L-carntine but not L-carnitine. Thus, acetyl-L-carnitine effectively suppressed the oxidative stress in and around mitochondria thereby preventing mitochondrial signaling pathway leading to apoptosis.
 ...
PMID:Acetyl-L-carnitine suppresses apoptosis of thioredoxin 2-deficient DT40 cells. 1871 18

High fluence low-power laser irradiation (HF-LPLI) can induce cell apoptosis via the mitochondria/caspase-3 pathway. Here, we further investigated the mechanism involved in the apoptotic process in human lung adenocarcinoma cells (ASTC-a-1) at a laser irradiation fluence of 120 J/cm(2) (633 nm). Cytochrome c release was ascribed to mitochondrial permeability transition (MPT) because the release was prevented by cyclosporine (CsA), a specific inhibitor of MPT. Furthermore, mitochondrial permeability for calcein (approximately 620 Da) was another evidence for the MPT induction under HF-LPLI treatment. A high-level intracellular reactive oxygen species (ROS) generation was observed after irradiation. The photodynamically produced ROS caused onset of MPT, as the ROS scavenger docosahexaenoic acid (DHA) prevented the MPT. However, CsA failed to prevented cell death induced by HF-LPLI, indicating the existence of other signaling pathways. Following laser irradiation, Bax activation occurred after mitochondrial depolarization and cytochrome c release, indicating Bax activation was a downstream event. In the presence of CsA, Bax was still activated at the end-stage of apoptotic process caused by HF-LPLI, suggesting that Bax was involved in an alternative-signaling pathway, which was independent of MPT. Under HF-LPLI treatment, cell viabilities due to pre-treatment with DHA, CsA, or Bax small interfering RNA (siRNA) demonstrated that the MPT signaling pathway was dominant, while Bax signaling pathway was secondary, and more importantly ROS mediated both pathways. Taken together, these results showed that HF-LPLI induced cell apoptosis via the CsA-sensitive MPT, which was ROS-dependent. Furthermore, there existed a secondary signaling pathway through Bax activation. The observed link between MPT and triggering ROS could be a fundamental phenomenon in HF-LPLI-induced cell apoptosis.
 ...
PMID:High fluence low-power laser irradiation induces mitochondrial permeability transition mediated by reactive oxygen species. 1900 21

We have investigated how n-3 highly unsaturated fatty acids (HUFAs) in the diet affect fatty acid (FA) utilization, fat storage and oxidative stress (OS) in Atlantic salmon (Salmo salar) white adipose tissue (WAT). Four groups of Atlantic salmon were fed for 21 weeks on one of the four diets supplemented with 23% (of dry matter) lipid. Docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) levels increased from 10% of total FAs in the rapeseed oil (RO) diet, to 20% in the fish oil (FO) diet, and to 50% and 55% in the DHA-enriched and EPA-enriched diets, respectively. Increased dietary levels of n-3 HUFAs resulted in lower fat percentage in WAT. Furthermore, mitochondrial FA beta-oxidation activity was higher in the FO group than it was in the RO group. The relative levels of DHA and EPA in phospholipids (PLs) from WAT and mitochondrial membranes increased with the increasing dietary levels of these HUFAs. In general, the mitochondrial membrane PLs were characterised by lower relative levels of n-3 HUFAs and higher relative levels of linoleic acid (LA; 18:2 n-6) than WAT membrane PLs. The predominance of LA relative to n-3 HUFAs in mitochondrial membrane PLs may help to protect these PLs from peroxidation. Cytochrome c oxidase measurements revealed higher incidence of disrupted mitochondrial membranes in the DHA and EPA dietary groups than in the FO and RO dietary groups. This disruption further affected the mitochondrial function, resulting in a marked reduction in FA beta-oxidation capacities. The reduction in mitochondrial function and the increase in the activity of superoxide dismutase (SOD) in the DHA and EPA groups showed that high dietary dose of DHA and EPA resulted in oxidative stress (OS). The increased activity of caspase 3 in the high n-3 HUFA groups suggested the induction of apoptosis and increased incidence of cell death in WAT, which may be one of the factors explaining the lower fat percentage found in these groups.
 ...
PMID:N-3 HUFAs affect fat deposition, susceptibility to oxidative stress, and apoptosis in Atlantic salmon visceral adipose tissue. 1901 Apr 38


<< Previous 1 2 3 4 5 6 7 8 9 10