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)

Tritrichomonas foetus is a serious veterinary pathogen, causing bovine trichomoniasis, a sexually transmitted disease leading to infertility and abortion. T. foetus infects the mucosal surfaces of the reproductive tract. Infection with T. foetus leads to apoptotic cell death of bovine vaginal epithelial cells (BVECs) in culture. An affinity-purified cysteine protease (CP) fraction yielding on sodium dodecyl sulfate-polyacrylamide gel electrophoresis a single band with an apparent molecular mass of 30 kDa (CP30) also induces BVEC apoptosis. Treatment of CP30 with the protease inhibitors TLCK (Nalpha-p-tosyl-l-lysine chloromethyl ketone) and E-64 [l-trans-epoxysuccinyl-leucylamide-(4-guanido)-butane] greatly reduces induction of BVEC apoptosis. Matrix-assisted laser desorption ionization-time-of-flight MALDI-TOF mass spectrometry analysis of CP30 reveals a single peak with a molecular mass of 23.7 kDa. Mass spectral peptide sequence analysis of proteolytically digested CP30 reveals homologies to a previously reported cDNA clone, CP8 (D. J. Mallinson, J. Livingstone, K. M. Appleton, S. J. Lees, G. H. Coombs, and M. J. North, Microbiology 141:3077-3085, 1995). Induction of apoptosis is highly species specific, since the related human parasite Trichomonas vaginalis and associated purified CPs did not induce BVEC death. Fluorescence microscopy along with the Cell Death Detection ELISA(PLUS) assay and flow cytometry analyses were used to detect apoptotic nuclear condensation, DNA fragmentation, and changes in plasma membrane asymmetry in host cells undergoing apoptosis in response to T. foetus infection or incubation with CP30. Additionally, the activation of caspase-3 and inhibition of cell death by caspase inhibitors indicates that caspases are involved in BVEC apoptosis. These results imply that apoptosis is involved in the pathogenesis of T. foetus infection in vivo, which may have important implications for therapeutic interference with host cell death that could alter the course of the pathology in vivo.
 ...
PMID:Tritrichomonas foetus induces apoptotic cell death in bovine vaginal epithelial cells. 1521 60

Parvovirus B19 (B19 virus) can persist in multiple tissues and has been implicated in a variety of diseases, including acute fulminant liver failure. The mechanism by which B19 virus induces liver failure remains unknown. Hepatocytes are nonpermissive for B19 virus replication. We previously reported that acute fulminant liver failure associated with B19 virus infection was characterized by hepatocellular dropout. We inoculated both primary hepatocytes and the hepatocellular carcinoma cell line Hep G2 with B19 virus and assayed for apoptosis by using annexin V staining. Reverse transcriptase PCR analysis and immunofluorescence demonstrated that B19 virus was able to infect the cells and produce its nonstructural protein but little or no structural capsid protein. Infection with B19 virus induced means of 28% of Hep G2 cells and 10% of primary hepatocytes to undergo apoptosis, which were four- and threefold increases, respectively, over background levels. Analysis of caspase involvement showed that B19 virus-inoculated cultures had a significant increase in the number of cells with active caspase 3. Inhibition studies demonstrated that caspases 3 and 9, but not caspase 8, are required for B19 virus-induced apoptosis.
 ...
PMID:Parvovirus B19-induced apoptosis of hepatocytes. 1522 Apr 51

Streptococcus pneumoniae is the major pathogen of community-acquired pneumonia and one of the most common causes of death due to infectious diseases in industrialized countries. Lung epithelium lines the airways and constitutes the first line of innate defense against respiratory pathogens. Little is known about the molecular interaction of pneumococci with lung epithelial cells. Apoptosis of lung epithelium is involved in some bacterial lung infections. In this study different pneumococcal strains specifically induced either apoptotic or necrotic death of human alveolar and bronchial epithelial cells. Pneumococcus-induced apoptosis did not depend on the virulence factors pneumolysin and H(2)O(2). Apoptotic cells showed increased activity of caspases 6, 8, and 9 but not increased activity of caspase 3. Moreover, programmed cell death could be strongly reduced by a caspase 6 inhibitor and a pan-caspase inhibitor. Inhibitors of calpain and chymotrypsin- and trypsin-like proteases also reduced pneumococcus-induced apoptosis. Furthermore, pneumococcus-infected human alveolar epithelial cells showed Bid cleavage and reduced levels of Bcl2 and Bax. Overexpression of Bcl2 in these cells reduced apoptosis significantly. Thus, pneumococci induced apoptosis of human alveolar and bronchial epithelial cells. Programmed cell death was executed by caspase 6 and noncaspase proteases, but not by caspase 3, and could be blocked by overexpression of Bcl2.
 ...
PMID:Streptococcus pneumoniae-induced caspase 6-dependent apoptosis in lung epithelium. 1532 85

Infection of cattle or bovine cells with bovine herpesvirus 1 (BHV-1) leads to increased apoptosis. Previous studies indicated that BHV-1 infected cell protein 0 (bICP0), the major transcriptional regulatory protein of BHV-1, is toxic in transiently transfected cells. Point mutations within the zinc RING finger of bICP0 reduced toxicity and eliminated the ability of bICP0 to activate viral gene expression. In mouse neuroblastoma cells (neuro-2A) and bovine turbinate cells, bICP0 activated caspase 3, a key regulatory protein in the apoptotic pathway. A pro-apoptotic gene (Bax), but not bICP0, induced caspase 3 cleavage and activation by 8 h after transfection of neuro-2A cells. Conversely, bICP0 or the N-terminal 356 aa of bICP0 did not induce caspase 3 cleavage in neuro-2A cells until 30 h after transfection, suggesting that bICP0 stimulates caspase 3 cleavage by an indirect mechanism. These studies indicate that the toxic functions of bICP0 correlate with caspase 3 cleavage and activation.
 ...
PMID:Infected cell protein 0 encoded by bovine herpesvirus 1 can activate caspase 3 when overexpressed in transfected cells. 1555 24

To assess the role of insulin action and inaction in the liver, immortalized hepatocyte cell lines have been generated from insulin receptor substrate (IRS)-2(-/-) and wild-type mice. Using this model, we have recently demonstrated that the lack of IRS-2 in neonatal hepatocytes resulted in insulin resistance. In the current study, we show that immortalized neonatal hepatocytes undergo apoptosis on serum withdrawal, with caspase-3 activation and DNA laddering occurring earlier in the absence of IRS-2. Insulin rescued wild-type hepatocytes from serum withdrawal-induced caspase-3 activation and DNA fragmentation in a dose-dependent manner, but it failed to rescue hepatocytes lacking IRS-2. In IRS-2(-/-) cells, insulin failed to phosphorylate Bad. Furthermore, in these cells, insulin was unable to translocate Foxo1 from the nucleus to the cytosol. Adenoviral infection of wild-type cells with constitutively active Foxo1 (ADA) induced caspase-8 and caspase-3 activities, proapoptotic gene expression, DNA laddering and apoptosis. Dominant negative Foxo1 regulated the whole pathway in an opposite manner. Prolonged insulin treatment (24 hours) increased expression of antiapoptotic genes (Bcl-xL), downregulated proapoptotic genes (Bim and nuclear Foxo1), and decreased caspase-3 activity in wild-type hepatocytes but not in IRS-2(-/-) cells. Infection of IRS-2(-/-) hepatocytes with adenovirus encoding IRS-2 reconstituted phosphatidylinositol 3-kinase (PI 3-kinase)/Akt/Foxo1 signaling, restored pro- and antiapoptotic gene expression, and decreased caspase-3 activity in response to insulin, thereby blocking apoptosis. In conclusion, IRS-2 signaling is specifically required through PIP3 generation to mediate the survival effects of insulin. Epidermal growth factor, via PIP3/Akt/Foxo1 phosphorylation, was able to rescue IRS-2(-/-) hepatocytes from serum withdrawal-induced apoptosis, modulating pro- and anti-apoptotic gene expression and downregulating caspase-3 activity.
 ...
PMID:IRS-2 mediates the antiapoptotic effect of insulin in neonatal hepatocytes. 1556 1

Accumulating evidence suggests that glutamate plays a key role in the proliferation and invasion of glioblastoma tumors. Astrocytic tumors have been shown to release glutamate at high levels, which may stimulate tumor cell proliferation and motility via activation of glutamate receptors. Excess glutamate has also been found to facilitate tumor invasion by causing excitotoxic damage to normal brain thereby paving a pathway for tumor migration. Results from tissue microarray analyses showed decreased excitatory amino acid transporter-2 (EAAT-2) expression in high-grade glial tumors compared with low-grade astrocytomas and normal brain. EAAT-2 expression was inversely correlated with tumor grade, implicating its potential role in glial tumor progression, which was reflected by an undetectable level of EAAT-2 protein in glioma cell lines. In this study, we sought to investigate the effect of reconstituted EAAT-2 on glioma cell growth in vitro and in vivo by adenoviral-mediated gene transfer. Infection of glioma cells with Ad-EAAT-2 resulted in a physiologic level of functional EAAT-2, and a subsequent dose-dependent reduction in cell proliferation in all glioma cell lines tested compared with controls. Interestingly, results from analyses of Annexin V staining, detection of poly(ADP-ribose)polymerase cleavage and caspase-3 activation all indicated that Ad-EAAT-2 infection elicited apoptosis in glioma cells. Ex vivo experiments in nude mice showed a total suppression of tumor growth at sites that received Ad-EAAT-2-infected cells. Collectively, our results uncovered a new function of EAAT-2 in controlling glioma proliferation. Further studies will improve our knowledge of the role of glutamate in glioma growth and may provide useful prognostic information and alternative therapeutic targets for the treatment of glioma.
 ...
PMID:The excitatory amino acid transporter-2 induces apoptosis and decreases glioma growth in vitro and in vivo. 1575 93

Reoviruses have provided insight into the roles played by specific viral genes and the proteins they encode in virus-induced cell death and tissue injury. Apoptosis is a major mechanism of cell death induced by reoviruses. Reovirus-induced apoptosis involves both death-receptor and mitochondrial cell death pathways. Reovirus infection is associated with selective activation of mitogen activated protein kinase (MAPK) cascades including JNK/SAPK. Infection also perturbs transcription factor signaling resulting in the activation of c-Jun and initial activation followed by strain-specific inhibition of NF-kappaB. Infection results in changes in the expression of genes encoding proteins involved in cell cycle regulation, apoptosis, and DNA damage and repair processes. Apoptosis is a major mechanism of reovirus-induced injury to key target organs including the CNS and heart. Inhibition of apoptosis through the use of caspase or calpain inhibitors, minocycline, or in caspase 3(-/-) mice all reduce virus-associated tissue injury and enhance survival of infected animals. Reoviruses induce apoptotic cell death (oncolysis) in a wide variety of cancer cells and tumors. The capacity of reoviruses to grow efficiently in transformed cells is enhanced by the presence of an activated Ras signaling pathway likely through mechanisms involving inhibition of antiviral PKR signaling and activation of Ras/RalGEF/p38 pathways. The potential of reovirus-induced oncolysis in therapy of human cancers is currently being investigated in phase I/II clinical trials.
 ...
PMID:Mechanisms of reovirus-induced cell death and tissue injury: role of apoptosis and virus-induced perturbation of host-cell signaling and transcription factor activation. 1580 55

Overexpression of NF-kappa B reportedly plays anti-apoptotic roles in the growth of AML cells. Control of AML cell growth was attempted using a replication-defective herpes simplex virus-1 vector, T0I kappa B alpha, overexpressing mutant I kappa B alpha to inhibit NF-kappa B in vitro. T0I kappa B alpha displays defective ICP4/ICP22/ICP27, isogenic thymidine kinase, and mutant I kappa B alpha. T0Z.1 expressing lacZ instead of I kappa B was used for controls. Infection of T0I kappa B alpha at 15 multiplicity of infection (MOI) with cells of AML lines, HL60, K562, and NB4 displaying >90% infection efficiency and tumor killing in vitro. Use of 10 microM of Ara-C alone was clinically equivalent to high-dose Ara-C, displaying 11% tumor killing. Neither ganciclovir (GCV) nor Ara-C enhanced T0I kappa B- alpha mediated tumor killing. Attenuation of NF-kappa B by T0I kappa B alpha was confirmed by EMSA. T0I kappa B alpha induced caspase-3 activity, with subsequent apoptosis confirmed by colorimetric and TUNEL assays. Fresh AML cells from 8 patients were infected with T0I kappa B alpha at 3 MOI, with or without GCV or 10 microM of Ara-C in vitro. Infection efficiency was 10%. T0I kappa B alpha displayed 8-15% tumor killing, superior to Ara-C in 6 of the 8 patients. Administration of Ara-C enhanced tumor killing in 5 of these 6 cases. Our results suggest that T0I kappa B alpha-mediated gene therapy induces apoptosis of AML cells in vitro.
 ...
PMID:I kappa B-mediated apoptotic gene therapy against acute myelogenous leukemia using replication-defective HSV-1 vector expressing TK and mutant I kappa B alpha. 1617 66

Periodontitis, a common infectious disease, is initiated by various gram-negative bacteria and characterized by the destruction of the periodontal tissue. Here, we investigated the role of caspases, intracellular proteases that are the key mediators of apoptosis. We show that activation of caspase-3 and caspase-7 is considerably enhanced in gingival tissue from patients with periodontitis. We also demonstrate in in vitro experiments that various periodontopathic bacteria exert a direct growth-suppressing effect and, moreover, can trigger a host-mediated cytotoxic activity involving the CD95 death receptor. Our data suggest that caspase activation is a prominent feature in periodontitis-associated tissue injury.
 ...
PMID:Caspase activation is involved in chronic periodontitis. 1621 96

Many viruses have evolved strategies to counteract cellular immune responses, including apoptosis. Vaccinia virus, a member of the poxvirus family, encodes an antiapoptotic protein, F1L. F1L localizes to mitochondria and inhibits apoptosis by preventing the release of cytochrome c by an undetermined mechanism (S. T. Wasilenko, T. L. Stewart, A. F. Meyers, and M. Barry, Proc. Natl. Acad. Sci. USA 100:14345-14350, 2003; T. L. Stewart, S. T. Wasilenko, and M. Barry, J. Virol. 79:1084-1098, 2005). Here, we show that in the absence of an apoptotic stimulus, F1L associates with Bak, a proapoptotic member of the Bcl-2 family that plays a pivotal role in the release of cytochrome c. Cells infected with vaccinia virus were resistant to Bak oligomerization and the initial N-terminal exposure of Bak following the induction of apoptosis with staurosporine. A mutant vaccinia virus missing F1L was no longer able to inhibit apoptosis or Bak activation. In addition, the expression of F1L was essential to inhibit tBid-induced cytochrome c release in both wild-type murine embryonic fibroblasts (MEFs) and Bax-deficient MEFs, indicating that F1L could inhibit apoptosis in the presence and absence of Bax. tBid-induced Bak oligomerization and N-terminal exposure of Bak in Bax-deficient MEFs were inhibited during virus infection, as assessed by cross-linking and limited trypsin proteolysis. Infection with the F1L deletion virus no longer provided protection from tBid-induced Bak activation and apoptosis. Additionally, infection of Jurkat cells with the F1L deletion virus resulted in cellular apoptosis, as measured by loss of the inner mitochondrial membrane potential, caspase 3 activation, and cytochrome c release, indicating that the presence of F1L was pivotal for inhibiting vaccinia virus-induced apoptosis. Our data indicate that F1L expression during infection inhibits apoptosis and interferes with the activation of Bak.
 ...
PMID:The vaccinia virus F1L protein interacts with the proapoptotic protein Bak and inhibits Bak activation. 1625 38


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