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: UNIPROT:P42574 (caspase-3)
45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor I (IGF-I) is an important survival growth factor that has been shown to inhibit apoptosis, but the effects of IGF-I on apoptotic signaling remain largely unknown. To investigate IGF-I actions on apoptosis of H9C2 cardiac muscle cells, we have defined the effects of IGF-I on Bcl-2, Bax, caspase 3, DNA fragmentation, and cell survival. The abundance of Bcl-2 and Bax was determined with immunoblotting, and the activities of caspase 3 were assayed with the labeled substrate DEVD-p-nitroanilide. The occurrence of apoptosis was determined by electrophoresis of labeled DNA fragments and by in situ terminal deoxynucleotidyl transferase UTP nick end labeling assay. We found that apoptosis of H9C2 cells, induced by serum withdrawal and doxorubicin, was associated with the induction of Bax and the activation of caspase 3. IGF-I partially inhibited Bax induction, caspase 3 activation, DNA fragmentation, and enhanced cell survival. Interestingly, there is a compensatory rise in the abundance of Bcl-2 upon serum withdrawal and doxorubicin treatment, and IGF-I stimulation resulted in decreased induction of Bcl-2. These results suggest that serum withdrawal- and doxorubicin-induced apoptosis of H9C2 cells probably in part resulted from induction of Bax and caspase 3, and IGF-I inhibited apoptosis by attenuating Bax induction and caspase 3 activation.
...
PMID:Insulin-like growth factor I modulates induction of apoptotic signaling in H9C2 cardiac muscle cells. 949 72

Aging is characterized by increased T cell lymphopenia, T cell dysfunction, and increased serum TNF levels. In this study, we have examined the role of TNF-induced apoptosis in T cell deficiency in lymphocytes from aged humans. The constitutive expression of TNF receptors (TNFRI and TNFRII) and the adapter molecules, including TNFR-associated death domain protein (TRADD), TNFR-associated factor 2 (TRAF-2), and receptor interacting protein (RIP), were analyzed both at the protein level by flow cytometry or Western blotting, and at the mRNA level using quantitative PCR or Northern blotting in lymphocytes from aged and young subjects. The susceptibility of T cells to undergo TNF-induced apoptosis was analyzed using terminal deoxynucleotidyltransferase-mediated UTP-end-labeling (TUNEL) and DNA ladder assays. Caspase (caspase-8 and caspase-3) activation was compared between aged and young subjects using Western blotting and colorimetric assays. In lymphocytes from aged humans, there was an increased susceptibility of CD4+ and CD8+ T cells to undergo TNF-alpha-induced apoptosis, as observed by TUNEL assay and DNA fragmentation ladder assay. Increased TNF-alpha-induced apoptosis was also observed in both CD45RA+ and CD45RO+ T cells from aging subjects. An increased constitutive expression of TNFRI and TRADD and decreased expression of TNFRII and TRAF-2 were observed in lymphocytes from aged as compared with young controls. In addition, there was an early and increased activation of caspases (caspase-8 and caspase-3) involved in TNFR/TNF signaling pathway, as evident by early cleavage of caspase-8, poly(ADP-ribose) polymerase (PARP), and caspase-3 substrate DEVD-p-nitroamilide NA. These data suggest that an increased TNF-alpha-induced apoptosis may play a role in T cell deficiency associated with human aging.
...
PMID:Increased TNF-alpha-induced apoptosis in lymphocytes from aged humans: changes in TNF-alpha receptor expression and activation of caspases. 997 90

A number of studies have provided evidence that neuronal cell loss after stroke involves programmed cell death or apoptosis. In particular, recent biochemical and immunohistochemical studies have demonstrated the expression and activation of intracellular proteases, notably caspase-3, which act as both initiators and executors of the apoptotic process. To further elucidate the involvement of caspases in neuronal cell death induced by focal stroke we developed a panel of antibodies and investigated the spatial and temporal pattern of both caspase-8 and caspase-3 expression. Our efforts focused on caspase-8 because its "apical" position within the enzymatic cascade of caspases makes it a potentially important therapeutic target. Constitutive expression of procaspase-8 was detectable in most cortical neurons, and proteolytic processing yielding the active form of caspase-8 was found as early as 6 hr after focal stroke induced in rats by permanent middle cerebral artery occlusion. This active form of caspase-8 was predominantly seen in the large pyramidal neurons of lamina V. Active caspase-3 was evident only in neurons located within lamina II/III starting at 24 hr after injury and in microglia throughout the core infarct at all times examined. Terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling, gel electrophoresis of DNA, and neuronal cell quantitation indicated that there was an early nonapoptotic loss of cortical neurons followed by a progressive elimination of neurons with features of apoptosis. These data indicate that the pattern of caspase expression occurring during delayed neuronal cell death after focal stroke will vary depending on the neuronal phenotype.
...
PMID:Caspase-8 and caspase-3 are expressed by different populations of cortical neurons undergoing delayed cell death after focal stroke in the rat. 1040 32

p53 is a pivotal molecule regulating the death of neurons both after acute injury and during development. The molecular mechanisms by which p53 induces apoptosis in neuronal cells, however, are not well understood. We have shown previously that adenovirus-mediated p53 gene delivery to neurons was sufficient to induce apoptosis. In the present study we have examined the molecular mechanism by which p53 evokes neuronal cell death. Adenovirus-mediated delivery of p53 to cerebellar granule neurons resulted in caspase-3 (CPP32) activation followed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) staining and loss of viability as determined by an MTT survival assay. To determine whether Bax is essential for caspase-3 activation, p53 was expressed in Bax-deficient cells. Bax null neurons did not exhibit caspase-3 activation in response to p53 and were protected from apoptosis. To determine whether Bax-dependent caspase-3 activation was required in p53-mediated neuronal cell death, caspase-3-deficient neurons were examined. Our results indicate that caspase-3-deficient neurons exhibit a remarkable delay in apoptosis and a dramatic decrease in TUNEL-positive cells. These studies demonstrate that p53-induced cell death in postmitotic neurons involves a Bax-dependent caspase-3 activation, suggesting that these molecules are important determinants in neuronal cell death after injury.
...
PMID:Bax-dependent caspase-3 activation is a key determinant in p53-induced apoptosis in neurons. 1047 88

Stimulation of beta-adrenergic receptor normally results in signaling by the heterotrimeric G protein G(s), leading to the activation of adenylyl cyclase, production of cAMP, and activation of cAMP-dependent protein kinase (PKA). Here we report that cell death of thymocytes can be induced after stimulation of beta-adrenergic receptor, or by addition of exogenous cAMP. Apoptotic cell death in both cases was observed with the appearance of terminal deoxynucleotidyl transferase-mediated UTP end labeling reactivity and the activation of caspase-3 in S49 T cells. Using thymocytes deficient in either Galpha(s) or PKA, we find that engagement of beta-adrenergic receptors initiated a Galpha(s)-dependent, PKA-independent pathway leading to apoptosis. This alternative pathway involves Src family tyrosine kinase Lck. Furthermore, we show that Lck protein kinase activity can be directly stimulated by purified Galpha(s). Our data reveal a new signaling pathway for Galpha(s), distinct from the classical PKA pathway, that accounts for the apoptotic action of beta-adrenergic receptors.
...
PMID:Apoptotic signaling through the beta -adrenergic receptor. A new Gs effector pathway. 1076 82

This study was designed to determine the direct cytotoxic effect of cocaine on human coronary artery endothelial cells (HCAECs). Cocaine treatment of cultured HCAECs induced a time- and dose-dependent increase in apoptotic cell death in HCAECs. Cocaine-induced surface exposure of phosphatidylserine in HCAECs was seen as early as at 6 h. With prolonged treatment < or =72 h, cocaine (10-500 microM) produced a dose-dependent increase in apoptosis in the cells. Corresponding DNA fragmentation induced by cocaine was demonstrated in situ by terminal deoxynucleotidyl transferase (Tdt) UTP nick end-labeling TUNEL assay and by electrophoresis of labeled DNA fragments, showing the characteristic apoptotic ladders. Both caspase-9 (Z-LEHD-FMK) and caspase-3 (Ac-DEVD-CHO) inhibitors blocked cocaine-induced apoptosis. In addition, cyclosporin A inhibited cocaine-induced apoptosis in a concentration-dependent manner with a median inhibitory concentration (IC50) of 0.3 microM. The maximum of 62% inhibition was obtained with 3 microM cyclosporin A. Cocaine-induced apoptosis also was blocked by naloxone and nifedipine in a dose-dependent manner. These findings suggest that cocaine induces apoptosis in cultured HCAECs, which may be mediated by opioid receptors. The release of cytochrome c from the mitochondria and its subsequent activation of caspase-9 and caspase-3 may play a key role in cocaine-induced apoptosis.
...
PMID:Cocaine induces apoptosis in human coronary artery endothelial cells. 1077 88

Previous studies have shown that ethane dimethanesulfonate (EDS) causes the apoptotic death of Leydig cells. The molecular mechanism by which EDS elicits its effect remains uncertain. The present study tested the hypothesis that caspase-3 is involved in the EDS-induced death of rat Leydig cells. Leydig cells were isolated from adult Sprague Dawley at 3, 6, 12, or 24 h after the rats received an EDS injection. Low mol wt DNA fragments that are characteristic of apoptosis were evident by 12 h post-EDS, and the ladder pattern was more pronounced at 24 h. During this same time period, the number of terminal deoxynucleotidyltransferase-mediated deoxy-UTP-biotin nick end labeling (TUNEL)-positive cells increased. Western blot analysis revealed that procaspase-3 was present only at low levels in control Leydig cells, and increased through 6 h post-EDS. By 12 h, procaspase-3 was reduced, whereas the cleaved, active caspase-3 forms appeared at 12 h and increased through 24 h post-EDS. Caspase-3 activity was blocked by caspase-3 inhibitor. In vitro, EDS treatment induced Leydig cell apoptosis. In the presence of cell-permeable caspase-3 inhibitor, however, apoptosis was significantly suppressed, providing further evidence for the involvement of caspase-3 in EDS-induced Leydig cell apoptotic death. Immunohistochemical analysis revealed weak staining for caspase-3 in the cytoplasm of control Leydig cells. From 12-24 h post-EDS, the time interval during which the active forms of caspase-3 appeared, caspase-3 immunoreactivity increased and became localized to the nuclei. Apoptosis and caspase-3 were colocalized in Leydig cells by a histological method that combined TUNEL and caspase-3 immunohistochemistry. In these studies, TUNEL-positive cells all exhibited intense nuclear caspase-3 immunoreactivity, whereas TUNEL-negative cells exhibited weak caspase-3 immunoreactivity in the cytoplasm. Taken together, these results indicate that Leydig cell apoptosis induced by EDS is mediated by caspase-3 activation, and suggest that the translocation of the active caspase-3 forms to the nucleus may be involved.
...
PMID:Caspase-3 activation is required for Leydig cell apoptosis induced by ethane dimethanesulfonate. 1080 95

Birth asphyxia can cause moderate to severe brain injury. It is unclear to what degree apoptotic or necrotic mechanisms of cell death account for damage after neonatal hypoxia-ischemia (HI). In a 7-d-old rat HI model, we determined the contributions of apoptosis and necrosis to neuronal injury in adjacent Nissl-stained, hematoxylin and eosin-stained, and terminal deoxynucleotidyl transferase-mediated UTP nick end-labeled sections. We found an apoptotic-necrotic continuum in the morphology of injured neurons in all regions examined. Eosinophilic necrotic neurons, typical in adult models, were rarely observed in neonatal HI. Electron microscopic analysis showed "classic" apoptotic and necrotic neurons and "hybrid" cells with intermediate characteristics. The time course of apoptotic injury varied regionally. In CA3, dentate gyrus, medial habenula, and laterodorsal thalamus, the density of apoptotic cells was highest at 24-72 hr after HI and then declined. In contrast, densities remained elevated from 12 hr to 7 d after HI in most cortical areas and in the basal ganglia. Temporal and regional patterns of neuronal death were compared with expression of caspase-3, a cysteine protease involved in the execution phase of apoptosis. Immunocytochemical and Western blot analyses showed increased caspase-3 expression in damaged hemispheres 24 hr to 7 d after HI. A p17 peptide fragment, which results from the proteolytic activation of the caspase-3 precursor, was detected in hippocampus, thalamus, and striatum but not in cerebral cortex. The continued expression of activated caspase-3 and the persistence of cells with an apoptotic morphology for days after HI suggests a prolonged role for apoptosis in neonatal hypoxic ischemic brain injury.
...
PMID:Apoptosis has a prolonged role in the neurodegeneration after hypoxic ischemia in the newborn rat. 1105 Jan 20

The ubiquitin proteasome system is responsible for the proteolysis of important cell cycle and apoptosis-regulatory proteins. In this paper we report that the dipeptidyl proteasome inhibitor, phthalimide-(CH2)8CH-(cyclopentyl) CO-Arg(NO2)-Leu-H (CEP1612), induces apoptosis and inhibits tumor growth of the human lung cancer cell line A-549 in an in vivo model. In cultured A-549 cells, CEP1612 treatment results in accumulation of two proteasome natural substrates, the cyclin-dependent kinase inhibitors p21WAF1 and p27KIP1, indicating its ability to inhibit proteasome activity in intact cells. Furthermore, CEP1612 induces apoptosis as evident by caspase-3 activation and poly(ADP-ribose) polymerase cleavage. Treatment of A-549 tumor-bearing nude mice with CEP1612 (10 mg/kg/day, i.p. for 31 days) resulted in massive induction of apoptosis and significant (68%; P < 0.05) tumor growth inhibition, as shown by terminal deoxynucleotidyltransferase-mediated UTP end labeling. Furthermore, immunostaining of tumor specimens demonstrated in vivo accumulation of p21WAF1 and p27KIP1 after CEP1612 treatment. The results suggest that CEP1612 is a promising candidate for further development as an anticancer drug and demonstrate the feasibility of using proteasome inhibitors as novel antitumor agents.
...
PMID:CEP1612, a dipeptidyl proteasome inhibitor, induces p21WAF1 and p27KIP1 expression and apoptosis and inhibits the growth of the human lung adenocarcinoma A-549 in nude mice. 1124 20

Curcumin, a major active component of turmeric, has been recognized as an anticarcinogenic agent because of its propensity to induce apoptosis in vivo and in vitro. Previously, we showed that curcumin protects cells against oligonucleosomal DNA fragmentation and induces a novel apoptosis-like pathway in Jurkat cells (Piwocka et al. Exp Cell Res 249, 299-307, 1999). Here, we have studied the ability of curcumin to induce cell death in other human and rodent transformed as well as normal cells. Normal cells were quiescent or stimulated to proliferate. We showed that 50 microM pigment is able to induce cell death in all studied cells, but cell death symptoms varied for different cells. All the cells died as assessed by the TdT-mediated UTP nick end labeling method or trypan blue exclusion test. No one type of cells showed oligonucleosomal DNA fragmentation (DNA "ladder") due to curcumin action, although in HL-60 cells, we were able to observe sub-G1 formation and caspase-3 activation. Together, these data showed that curcumin induces cell death in all tested cells that can be classified as apoptosis-like, and only in HL-60 cells can it be recognized as classical apoptosis.
...
PMID:Effect of curcumin on the apoptosis of rodent and human nonproliferating and proliferating lymphoid cells. 1134 Oct 39


1 2 3 4 5 6 7 8 9 Next >>

---