Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.4.22.56 (caspase-3)
35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pituitary adenylate cyclase activating polypeptide (PACAP), vasoactive intestinal peptide (VIP) and peptide histidine-isoleucine (PHI), are structurally related endogenous peptides widely expressed in the central and peripheral nervous system and showing rich profile of biological activities. They act as neurotransmitters, neuromodulators and neurotrophic factors. Recently, their neuroprotective potential has been revealed in numerous in vitro and in vivo models. Thus, PACAP and VIP protected the cells from neurotoxic effects of ethanol, hydrogen peroxide (H2O2, beta-amyloid and glycoprotein 120 (gp120). Moreover, PACAP showed neuroprotection against glutamate, human prion protein fragment 106-126 [PrP(106-126)] and C2-ceramide. Both peptides reduced brain damage after ischemia and ameliorated neurological deficits in a model of Parkinson's disease. Neuroprotective potential of PHI has not been thoroughly investigated yet, but several results obtained in the last years do not exclude it. The mechanism underlying neuroprotective properties of PACAP seems to involve activation of adenylyl cyclase (AC) --> cyclic adenosine 3',5'-mono-phosphate (cAMP) --> protein kinase A (PKA) and mitogen-activated protein (MAP) kinase pathways, and inhibition of caspase-3. PACAP can also, yet indirectly, stimulate astrocytes to release neuroprotective factors, such as regulated upon activation normal T cell expressed and secreted (RANTES) and macrophage inflammatory protein 1 (MIP-1) chemokines. Neuroprotective activity of VIP seems to involve an indirect mechanism requiring astrocytes. VIP-stimulated astrocytes secrete neuroprotective proteins, including activity-dependent neurotrophic factor (ADNF) and activity-dependent neuroprotective protein (ADNP), as well as a number of cytokines. However, in the activated microglia, VIP and PACAP are capable of inhibiting the production of inflammatory mediators which can lead to neurodegenerative processes within the brain. In conclusion, studies carried out on the central nervous system have shown that PACAP, VIP, and likely PHI, are endowed with a neuroprotective potential, which renders them (or their derivatives) promising therapeutic agents in several psychoneurological disorders linked to neurodegeneration.
...
PMID:Neuroprotective potential of three neuropeptides PACAP, VIP and PHI. 1598 13

It has been proposed that direct and indirect mechanisms contribute to the unresolved issue of CD4(+) T-cell depletion that results from HIV-1 infection. We recently reported that plasma levels of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) are elevated in HIV-1-infected patients and that they correlate with viral load. The present study investigates the expression of TRAIL death receptor 5 (DR5) in the peripheral-blood mononuclear cells (PBMCs) of HIV-1-infected patients and its role in CD4(+) T-cell death. DR5 expression was elevated and associated with the apoptotic marker annexin V. Apoptosis was reduced in CD4(+) T cells when cultured with anti-DR5 antibody. CD4(+), but not CD8(+), T cells from uninfected donors expressed TRAIL, DR5, and activated caspase-3 when cultured with infectious or noninfectious HIV-1, resulting in preferential apoptosis of CD4(+) T cells. TRAIL, caspase-3 expression, and apoptosis were type 1 interferon (IFN) dependent. Induction of apoptosis and DR5 expression required glycoprotein 120 (gp120)-CD4 interaction. Finally, we analyzed DR5 expression by CD4(+) T cells in highly active antiretroviral therapy (HAART)-treated patients. The decreased viral loads and increased CD4 counts of HAART-responsive patients were associated with a decrease in DR5 mRNA expression by CD4(+) T lymphocytes. We propose a novel model in which a type 1 IFN-regulated TRAIL /DR5 mechanism induces apoptosis of HIV-1-exposed CD4(+) T cells.
...
PMID:CD4+ T-cell death induced by infectious and noninfectious HIV-1: role of type 1 interferon-dependent, TRAIL/DR5-mediated apoptosis. 1604 22

This study was carried out to investigate apoptotic effects of the glycoprotein (SNL glycoprotein, 150 kDa) isolated from Solanum nigrum Linne, which has been used as an anti-pyretic and anti-cancer agent in folk medicine. We found that the SNL glycoprotein consists of carbohydrate (69.74%) and protein content (30.26%), which has >50% hydrophobic amino acids containing glycine and proline. LDH assay indicated that the SNL glycoprotein has obvious cytotoxic and apoptotic effects (>50% cell death) at 40 microg/ml SNL glycoprotein for 2 h in HT-29 cells. The results showed that the SNL glycoprotein has a stimulatory effect on the release of mitochondrial cytochrome c, cleavages of pro-caspase-9, pro-caspase-3, and poly(ADP-ribose) polymerase (PARP) proteins in HT-29 cells. However, the SNL glycoprotein did not significantly stimulate or change the levels of intracellular reactive oxygen species (ROS). The results of this experiment suggest that the SNL glycoprotein activates caspase-3 in HT-29 cells, independent of ROS.
...
PMID:Glycine- and proline-rich glycoprotein isolated from Solanum nigrum Linne activates caspase-3 through cytochrome c in HT-29 cells. 1607 93

Apoptotic loss of CD4+ T cells has been proposed as a mechanism of T cell depletion in human immunodeficiency virus (HIV) infections resulting in immunodeficiency. The Env glycoprotein has been implicated in apoptosis of uninfected bystander cells via gp120 binding to CD4/CXC chemokine receptor 4 as well as the fusion/hemifusion process mediated by gp41. Using an in vitro model of coculture of Env-expressing cells as effectors and CD4+ T cells as targets, we find that apoptosis mediated by Env glycoprotein in bystander cells in fact correlates with gp41-induced hemifusion. Further, the apoptotic pathway initiated by this interaction involves caspase-3-dependent mitochondrial depolarization and reactive oxygen species production. HIV gp41-induced mitochondrial depolarization is inhibited by protease inhibitor nelfinavir but not by other HIV protease inhibitors or inhibitors of calpain and cathepsin. This "kiss of death" (hemifusion) signaling pathway is independent of p38 mitogen-activated protein kinase and p53, making it distinct from the apoptosis seen in syncytia. We also show that virion-induced apoptosis is gp41-dependent. Our findings provide new insights into the mechanism via which HIV gp41 mediates apoptosis in bystander cells.
...
PMID:HIV gp41-induced apoptosis is mediated by caspase-3-dependent mitochondrial depolarization, which is inhibited by HIV protease inhibitor nelfinavir. 1633 May 30

Overexpression of extracellular matrix metalloproteinase inducer (EMMPRIN or CD147), a member of the immunoglobulin family and a glycoprotein enriched on the surface of tumor cells, promotes invasion, metastasis, and growth and survival of malignant cells and confers resistance to some chemotherapeutic drugs. However, the molecular mechanisms underlying the actions of EMMPRIN are not fully understood. In this study we sought to determine whether EMMPRIN contributes to the malignant phenotype of breast cancer by inhibiting anoikis, a form of apoptosis induced by loss or alteration of cell-cell or cell-matrix anchorage, and to explore the signaling pathways involved. We found that in the absence of attachment, human breast carcinoma cells expressing high levels of EMMPRIN formed less compact aggregates with larger surface area and less fibronectin matrix assembly, had higher viability, and were resistant to anoikis. Knockdown of EMMPRIN expression by RNA interference (small interfering RNA or short hairpin RNA) sensitized cancer cells to anoikis, as demonstrated by activation of caspase-3, increased DNA fragmentation, and decreased cellular viability. Furthermore, we observed that the accumulation of Bim, a proapoptotic BH3-only protein, was reduced in EMMPRIN-expressing cells and that silencing of EMMPRIN expression elevated Bim protein levels and enhanced cellular sensitivity to anoikis. Treatment of cells with a MEK inhibitor (U0126) or proteasome inhibitor (epoxomicin) also up-regulated Bim accumulation and rendered cells more sensitive to anoikis. These results indicated that expression of EMMPRIN protects cancer cells from anoikis and that this effect is mediated at least in part by a MAP kinase-dependent reduction of Bim. Because anoikis deficiency is a key feature of neoplastic transformation and invasive growth of epithelial cancer cells, our study on the role of EMMPRIN in anoikis resistance and the mechanism involved underscores the potential of EMMPRIN expression as a prognostic marker and novel target for cancer therapy.
...
PMID:Extracellular matrix metalloproteinase inducer (CD147) confers resistance of breast cancer cells to Anoikis through inhibition of Bim. 1644 28

We have previously shown that injection of anti-glycoprotein (GP) IIb induces murine immune thrombocytopenia (ITP) and that intravenous immunoglobulin (IVIg) ameliorates ITP. We hypothesise that murine ITP may be associated with platelet apoptosis, which is upregulated by anti-GPIIb and downregulated by IVIg. The current study demonstrated that anti-GPIIb injection induced three critical apoptosis manifestations in platelets: (i) mitochondrial inner transmembrane potential (delta psi m) depolarisation; (ii) caspase-3 activation; and (iii) phosphatidylserine (PS) exposure. IVIg administration inhibited caspase-3 activation and PS exposure, but not delta psi m-depolarisation, in anti-GPIIb-treated platelets, demonstrating that IVIg ameliorates thrombocytopenia concomitantly with inhibiting late, but not early mechanisms of platelet apoptosis.
...
PMID:Intravenous immunoglobulin inhibits anti-glycoprotein IIb-induced platelet apoptosis in a murine model of immune thrombocytopenia. 1651 32

This study was carried out to investigate the apoptotic effects of glycoprotein (SNL glycoprotein, 150-kDa) isolated from Solanum nigrum Linne, which has been used as an antipyretic and anticancer agent in folk medicine. We found that SNL glycoprotein consists of carbohydrate content (69.74%) and protein content (30.26%), which contains more than 50% hydrophobic amino acids such as glycine and proline. SNL glycoprotein showed remarkable cytotoxic and apoptotic effects at 40 microg/ml of SNL glycoprotein for 4 h in HCT-116 cells. In the activity of the apoptotic related proteins [caspase-3 and poly(ADP-ribose)polymerase (PARP)], the results showed that SNL glycoprotein (40 microg/ml) has a stimulatory effect on caspase-3 activation and PARP cleavage in HCT-116 cells. Moreover, SNL glycoprotein blocked nuclear factor-kappa B (NF-kappaB) activation and reduced inducible nitric oxide (iNO) production. Interestingly, pyrrolidine dithiocarbamate (PDTC, for NF-kappaB inhibitor) and N omega-Nitro-L-arginine methylester hydrochloride (L-NAME, for NO inhibitor) effectively stimulated the caspase-3 activation in HCT-116 cells. The results in this experiment indicated that SNL glycoprotein induces apoptosis through the NF-kappaB activation and inducible nitric oxide (iNO) production in HCT-116 cells. Here, we speculate that SNL glycoprotein is one of the chemotherapeutic agents and of the modulators for apoptotic signals in HCT-116 cells.
...
PMID:150 kDa glycoprotein isolated from Solanum nigrum Linne stimulates caspase-3 activation and reduces inducible nitric oxide production in HCT-116 cells. 1652 44

In type 2B von Willebrand disease, there is spontaneous binding of mutated von Willebrand factor (VWF) multimers to platelets. Here we report a family in which severe thrombocytopenia may also be linked to abnormal megakaryocytopoiesis. A heterozygous mutation in the VWF A1 domain gave a R1308P substitution in an interactive site for glycoprotein Ibalpha (GPIbalpha). Electron microscopy showed clusters of platelets in close contact. Binding of antibodies to the GPIbalpha N-terminal domain was decreased, whereas GPIX and GPV were normally detected. In Western blotting (WB), GPIbalpha, alphaIIb, and beta3 were normally present. Proteins involved in Ca(2+) homeostasis were analyzed by quantitating platelet mRNA or by WB. Plasma membrane Ca(2+) ATPase (PMCA)-4b and type III inositol trisphosphate receptor (InsP(3)-R3) were selectively increased. The presence of degradation products of polyadenosine diphosphate (ADP)-ribose polymerase protein (PARP) suggested ongoing caspase-3 activity. These were findings typical of immature normal megakaryocytes cultured from peripheral blood CD34(+) cells with TPO. Significantly, megakaryocytes from the patients in culture produced self-associated and interwoven proplatelets. Immunolocalization showed VWF not only associated with platelets, but already on the megakaryocyte surface and within internal channels. In this family, type 2B VWD is clearly associated with abnormal platelet production.
...
PMID:Impaired megakaryocytopoiesis in type 2B von Willebrand disease with severe thrombocytopenia. 1672 Aug 32

Permeability-glycoprotein (Pgp) positive cells are known to be encoded by the multidrug-resistance gene (MDR1), and characterized by a reduced ability to accumulate drugs. The vinblastin-resistant, Pgp positive CEM-VLB 1000 and its wild type (Pgp-negative and vinblastin-sensitive) counterpart CEM-T4 human leukemia cells, when treated with the alkaloid sanguinarine, were both found to undergo apoptosis at concentrations of 1.5 microg/ml and oncosis/blister cell death (BCD) at concentrations of 12.5 microg/ml. The aim of this study was to assess the ability of sanguinarine to overcome Pgp-mediated multidrug-resistance (MDR), and also to characterize the cell death processes of apoptosis and oncosis (or bimodal cell death) induced by sanguinarine in MDR cells. The cell death processes of apoptosis and oncosis in CEM-VLB 1000 and CEM-T4 cell lines were found to be qualitatively similar when assessed by light microscopy, terminal deoxynucleotidyl transferase (TdT) end-labeling, annexin-V-binding, trypan blue exclusion and western blot analysis. Western blotting revealed an increase in the Bax/Bcl-2 ratio and activation of caspase-3 in apoptosis but not oncosis in both cell lines. The Pgp-positive CEM-VLB 1000 cells and their wild type CEM-T4 cells were both equally sensitive to sanguinarine. Thus, sanguinarine may overcome the phenomenon of Pgp-mediated MDR by inducing apoptosis through increasing the Bax/Bcl-2 ratio and activating caspase-3, and oncosis, which involved neither.
...
PMID:Sanguinarine overcomes P-glycoprotein-mediated multidrug-resistance via induction of apoptosis and oncosis in CEM-VLB 1000 cells. 1673 6

The effects of dietary corn bran hemicellulose (CBH) and neomycin (Neo) on hepatic caspase-3 activity and glycoprotein concentration were investigated to explore the possible mechanism of the alleviative action of dietary CBH and Neo on the development of D-galactosamine (GalN)-hepatitis. Rats were fed a diet containing 5% CBH with or without neomycin (Neo) for 7 or 14 d. On the last day of feeding, the rats were treated with GalN (400 mg/kg body weight, i.p.), and their plasma transaminase activities, hepatic glycoprotein concentrations and hepatic caspase-3 activities were determined 6 or 24 h later. Although the elevations of plasma transaminase activities were suppressed by CBH or Neo 24 h after GalN-treatment, the activities were not affected by CBH or Neo at an early stage (6 h) of GalN action. At 6 h, hepatic caspase-3 activity was elevated by CBH diet alone as high as that of the GalN-injected control-diet group, and the activity was not elevated further by GalN. At the same time, both GalN-treatment and CBH feeding reduced the hepatic glycoprotein (Mw. 64,000-74,000) concentration, but Neo did not affect the caspase activity or the glycoprotein concentration. These results suggest that dietary CBH elevates hepatic caspase-3 activity and reduces hepatic glycoprotein concentration, and may imply that CBH would suppress GalN-hepatitis not at the early- or middle-step of apoptosis but at the late-step of apoptosis or necrosis, although the relation between these phenomena and the alleviative effects of CBH and Neo on GalN-induced hepatitis is yet to be clarified.
...
PMID:Effects of dietary corn bran hemicellulose and neomycin on hepatic caspase-3 activity and glycoprotein concentration in rats treated with or without D-galactosamine. 1680 89


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

---