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 incidence of cancer increases with advancing age, but the biological behavior of cancer is known to be less aggressive in elderly people. Thus, the proliferative activity and extent of apoptosis of cancer cells were assessed in samples from 163 cases of colorectal cancer focusing on the age of patients, using Ki-67 labeling index (LI) and apoptotic index (AI) by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick end labeling method and staining for activated caspase-3. The Ki-67 LI of colorectal cancer ranged from 2.33 to 80.4% (mean 32.2%), while the AI ranged from 0.00 to 14.8% (mean 3.57%). Concerning the aging effect, linear and positive correlations were found for the Ki-67 LI of cancer with age (p<0.05) and the AI of cancer with age (p<0.05). However, in normal colorectal mucosa, aging of patients revealed a significant correlation only with the AI but not with the Ki-67 LI. The AI in earlier stages of cancers (stages 0 and 1) revealed a significant difference between younger cases (age<65) and more elderly cases (age>/=65) (p<0.05), however, the Ki-67 LI did not exhibit a significant difference. Therefore, an increased frequency of apoptosis in colorectal cancer tissues, especially in the earlier stages, may possibly explain the slower growth of colorectal cancers in the elderly. Next, the expressions of several regulatory molecules for the proliferation/apoptosis of tumor cells were determined. The results demonstrated a tendency for stronger and more frequent expressions of c-myc, Bak and Bax despite a rather weaker expression of Bcl-2 in cancer tissues from the elderly compared with those from the younger patients. The potential roles of these regulatory molecules on age-change in the proliferation/apoptosis of colorectal cancers are discussed.
 ...
PMID:Incidence of apoptosis increases with age in colorectal cancer. 1255 16

Extracellular ATP is a potent signaling factor that modulates a variety of cellular functions through the activation of P2 purinergic receptors. Extracellular ATP at higher concentrations exerts cytostatic as well as cytotoxic effects in a variety of cell systems, the mechanism of which is not fully understood. In this study, we used cultured human embryonic kidney (HEK) cells stably transfected with human P2X(7) receptors (HEK-P2X(7)) to investigate the mechanism of ATP-induced cell death. The cytotoxic effects of ATP in HEK-P2X(7) cells were dose- and time-dependent, whereas ADP, AMP, and UTP had no effect. ATP treatment induced a significant increase in apoptotic HEK-P2X(7) cells as ascertained by the terminal deoxynucleotidyl transferase dUTP nick-end labeling technique and flow cytometry. An ATP-induced decrease in the pro-apoptotic bax gene expression was detected by apoptosis-related cDNA microarray analysis, which correlated with a decrease of Bax protein expression. Western blot analysis revealed that ATP treatment resulted in the processing of pro-caspase 3 to its active form and cleavage of the nuclear enzyme, poly(ADP-ribose) polymerase (PARP). Both ATP-induced molecular alterations in HEK-P2X(7) cells (i.e., decrease of Bax expression and increase of PARP cleavage) were blocked by the purinergic P2X(7) receptor antagonist oxidized ATP. In conclusion, we demonstrated the importance of the P2X(7) receptor in ATP induced cell death of HEK-P2X(7) cells, which seems to be independent of bax expression; however, the activation of caspases is required.
 ...
PMID:Poly(ADP-ribose) polymerase activation and changes in Bax protein expression associated with extracellular ATP-mediated apoptosis in human embryonic kidney 293-P2X7 cells. 1260 81

This study examined the apoptotic mechanisms of macrophages following a lateral fluid percussive brain injury. A marked induction of inducible NO synthase (iNOS) immunoexpression was observed in brain macrophages in the subarachnoid space and lateral ventricles ipsilateral to the injury. Numerous apoptotic macrophages occurred in the same region 7 days after the injury as shown by in situ terminal transferase d-UTP nick-end labeling (TUNEL) and caspase-3 immunohistochemistry. Double immunofluorescence staining showed that only a small number of TUNEL positive cells were iNOS positive; many TUNEL positive cells, however, were observed in the vicinity of iNOS positive cells. Administration of aminoguanidine resulted in a marked reduction of apoptotic cells in the lesioned area suggesting that overproduction of NO is linked to diminution of brain macrophages by apoptosis.
 ...
PMID:Nitric oxide induces macrophage apoptosis following traumatic brain injury in rats. 1261 16

The physiological role of the uracil nucleotide-preferring P2Y(6) and P2Y(4) receptors is still unclear, although they are widely distributed in various tissues. In an effort to identify their biological functions, we found that activation by UDP of the rat P2Y(6) receptor expressed in 1321N1 human astrocytes significantly reduced cell death induced by tumor necrosis factor alpha (TNF alpha). This effect of UDP was not observed in non-transfected 1321N1 cells. Activation of the human P2Y(4) receptor expressed in 1321N1 cells by UTP did not elicit this protective effect, although both receptors were coupled to phospholipase C. The activation of P2Y(6) receptors prevented the activation of both caspase-3 and caspase-8 resulting from TNF alpha exposure. Even a brief (10-min) incubation with UDP protected the cells against TNF alpha-induced apoptosis. Interestingly, UDP did not protect the P2Y(6)-1321N1 cells from death induced by other methods, i.e. oxidative stress induced by hydrogen peroxide and chemical ischemia. Therefore, it is suggested that P2Y(6) receptors interact rapidly with the TNF alpha-related intracellular signals to prevent apoptotic cell death. This is the first study to describe the cellular protective role of P2Y(6) nucleotide receptor activation.
 ...
PMID:Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y6, but not P2Y4 nucleotide receptors. 1262 23

The present study examined the effects of a selective inducible nitric oxide synthase (iNOS) inhibitor, aminoguanidine (AG), on neuronal cell survival and post-traumatic recovery in rats following a lateral fluid percussive brain injury. Daily treatment of AG at the dosage of 100 mg/kg or normal saline was given intraperitoneally into rats starting 2 h before or 30 min after brain injury. Treatment with AG significantly reduced lesion volumes in the brains of rats after injury, as evaluated by high-resolution magnetic resonance imaging (MRI). Immunohistochemical analysis showed a marked induction of iNOS expression in brain macrophages ipsilateral to the injury. Apoptotic neurons were observed in the ipsilateral cerebral cortex by in situ terminal transferase d-UTP nick-end labelling (TUNEL) and caspase-3 immunohistochemistry. In rats receiving prophylactic or post-injury treatment of AG, the number of degenerating neurons was markedly reduced in the cerebrum compared to those receiving saline injection. The location and extent of these pathologic changes correlated with MRI findings. Neurobehavioral studies showed that rotametric performance, grip-strength score, total and ambulatory locomotor responses and acoustic startle response were reduced in rats subjected to the injury but were significantly improved in AG-treated rats. It is suggested that inhibition of iNOS by AG may represent a potential therapeutic strategy for the treatment of traumatic brain injury.
 ...
PMID:Neuroprotection by aminoguanidine after lateral fluid-percussive brain injury in rats: a combined magnetic resonance imaging, histopathologic and functional study. 1262 24

We have revealed previously that the survival rate of beta cells of cat retinal ganglion cells (RGCs) rapidly decreased to 29% on day 7 after optic nerve transection, whereas that of alpha cells slowly decreased to 64% on day 14 (Watanabe et al., 2001). The reason that beta cells die more rapidly than alpha cells was not clear. In the present study, we tested the possibility that the rapid death of beta cells is attributable to apoptosis, as shown for some axotomized RGCs in rats. The following results were obtained. First, the proportion of pyknotic cells in Nissl-stained cat retinas started to increase sharply starting on day 4 and reached a peak on day 6 after optic nerve transection. The time course of occurrence of pyknotic cells corresponded well with that of the rapid death of axotomized beta cells. Secondly, the proportion of pyknotic cells was the highest in the area centralis (AC), in which beta cells are densely distributed. The preferential death of axotomized RGCs in the AC was also confirmed by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining in cross sections. Thirdly, after the intravitreal injection of caspase 3 inhibitor (z-DEVD-cmk) the survival of axotomized beta cells on day 7 was significantly enhanced, whereas no such survival-promoting effect was obtained in axotomized alpha cells. Taken together, these results suggest that the rapid death of axotomized beta cells is attributable mainly to apoptosis, which is mediated by caspase 3.
 ...
PMID:Apoptotic death of beta cells after optic nerve transection in adult cats. 1276 88

We examined the expression of metabotropic glutamate (mGlu) receptors in species of fish that differ for their vulnerability to anoxic brain damage. Although expression of mGlu1a and mGlu5 receptors was similar in the brain of all species examined, expression of mGlu2/3 receptors was substantially higher in the brain of anoxia-tolerant species (i.e., the carp Carassius carassius and the goldfish Carassius auratus) than in the brain of species that are highly vulnerable to anoxic damage, such as the trouts Salmo trutta and Oncorhynchus mykiss. This difference was confirmed by measuring the mGlu2/3 receptor-mediated inhibition of forskolin-stimulated cAMP formation in slices prepared from the telencephalon of C. auratus and S. trutta. We exposed the goldfish C. auratus to water deprived of oxygen for 4 hr for the induction of hypoxic brain damage. Although the goldfish survived this treatment, the occurrence of apoptotic cell death could be demonstrated by terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining and by the assessment of caspase-3 activity in different brain region. The extent of cell death was highest in the medulla oblongata, followed by the optic tectum, cerebellum, and hypothalamus. No cell death was found in the telencephalon. This regional pattern of hypoxic damage was inversely related to the expression of mGlu2/3 receptors, which was lowest in the medulla oblongata and highest in the telencephalon. Treatment of the goldfish with the brain permeant mGlu2/3 receptor antagonist LY341495 (1 mg/kg, i.p.) amplified anoxic damage throughout the brain and enabled the induction of cell death by anoxia in the telencephalon. In contrast, treatment of the goldfish with the mGlu2/3 receptor agonist LY379268 (0.5 or 1 mg/kg, i.p.) was highly protective against anoxic brain damage. Finally, exposure to the antagonist LY341495 (0.5 microm) greatly amplified the release of glutamate induced by hypoxia in slices prepared from the medulla oblongata and the telencephalon of the goldfish. We conclude that expression of mGlu2/3 receptors provides a major defensive mechanism against brain damage in anoxia-tolerant species.
 ...
PMID:Group II metabotropic glutamate receptors regulate the vulnerability to hypoxic brain damage. 1285 20

Expression of heat shock proteins (HSPs) as a heat stress response is associated with acquisition of thermotolerance. Herbimycin A is a tyrosine kinase inhibitor that has been shown to induce HSPs. The present study aims to investigate the effects of herbimycin A on thermotolerance in rats subjected to heat stress exposure. Herbimycin A induced hsp70 to peak levels 12 h post-injection in rats without heat stress. No change in hsp70 levels was observed in the vehicle- and saline-treated rats. In rats exposed to heat stress at 45 degrees C for 25 min, 12 h post-treatment, lower peak temperatures were attained in herbimycin A-treated group as compared to the vehicle- and saline-treated groups. Terminal transferase-mediated d-UTP nick end labeling (TUNEL) showed that a significant decrease in apoptosis of hepatocytes in herbimycin A-treated rats as compared to the vehicle- and saline-treated rats. Caspase-3 activation was also lower in herbimycin A-treated rats, compared to the vehicle- and saline-treated rats. The present study has demonstrated that herbimycin A is effective for development of thermotolerance and therefore protects rats from heat stress.
 ...
PMID:Herbimycin A attenuates apoptosis during heat stress in rats. 1290 3

It has become clear that apoptosis is an essential part of normal folliculogenesis and that granulosa cells in particular demonstrate intense cellular activity as well as programmed cell death. Although the entire mechanism of apoptosis appears to be conserved through many species, it now becomes clear that different cells may use different pathways within this system. We examined human granulosa cells after ovulation induction during an in vitro fertilization procedure to study apoptosis in this particular situation. We demonstrated a loss of cytokeratin staining as granulosa cells differentiate. We also detected that granulosa cells with apoptotic morphology did not stain for terminal deoxy-UTP nick end labeling and we showed the absence of immunoreactivity for caspase-cleaved cytokeratin, caspase-cleaved poly-ADP-ribose polymerase and caspase-cleaved caspase-3 in apoptotic granulosa cells. These data provide strong arguments for a caspase-independent cell death mechanism in human granulosa-lutein cells.
 ...
PMID:Human granulosa cells after ovulation induction show caspase-independent cell death. 1293 44

Diadenosine tetraphosphate (AP4A), an endogenous diadenosine polyphosphate, reduces ischemic injury in the heart. In this study, we report the potent and protective effects of AP4A in rodent models of stroke and Parkinson's disease. AP4A, given intracerebroventricularly before middle cerebral artery (MCA) ligation, reduced cerebral infarction size and enhanced locomotor activity in adult rats. The intravenous administration of AP4A also induced protection when given early after MCA ligation. AP4A suppressed terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) induced by hypoxia/reperfusion in primary cortical cultures, and reduced both ischemia-induced translocation of mitochondrial cytochrome c and the increase in cytoplasmic caspase-3 activity in vivo. The purinergic P2/P4 antagonist di-inosine pentaphosphate or P1-receptor antagonist sulfonylphenyl theophylline, but not the P2-receptor antagonist suramin, antagonized the effect of AP4A, suggesting that the observed protection is mediated through an anti-apoptotic mechanism and the activation of P1- and P4-purinergic receptors. AP4A also afforded protection from toxicity induced by unilateral medial forebrain bundle injection of 6-hydroxydopamine (6-OHDA). One month after lesioning, vehicle-treated rats exhibited amphetamine-induced rotation. Minimal tyrosine hydroxylase immunoreactivity was detected in the lesioned nigra or striatum. No KCl-induced dopamine release was found in the lesioned striatum. All of these indices of dopaminergic degeneration were attenuated by pretreatment with AP4A. In addition, AP4A reduced TUNEL in the lesioned nigra 2 d after 6-OHDA administration. Collectively, our data suggest that AP4A is protective against neuronal injuries induced by ischemia or 6-OHDA through the inhibition of apoptosis. We propose that AP4A may be a potentially useful target molecule in the therapy of stroke and Parkinson's disease.
 ...
PMID:Diadenosine tetraphosphate protects against injuries induced by ischemia and 6-hydroxydopamine in rat brain. 1294 27


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