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

Ischemia-induced acute renal failure (ARF) is a disorder with high morbidity and mortality. ARF is characterized by a regeneration phase, yet its molecular basis is still under study. Changes in gene expression have been reported in ARF, and some of these genes are specific for nephrogenic processes. We tested the hypothesis that the regeneration process developed after ischemia-induced ARF can be characterized by the reexpression of important regulatory proteins of kidney development. The distribution pattern and levels of nephrogenic proteins in rat kidneys after ischemia were studied by immunohistochemistry and immunoblot analysis. Ischemic damage was assessed by conventional morphology, serum creatinine, and the apoptotic markers terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and caspase 3. The hypoxia levels induced by ischemia were assessed by specific markers: hypoxia induced factor (HIF)-1alpha and 2-pimonidazole. In kidneys with ARF, an important initial damage was observed through periodic acid Schiff staining, by the induction of damage markers alpha-smooth muscle actin (alpha-SMA) and macrophages (ED-1) and by apoptosis induction. In agreement with diminishing renal damage at the initial reparation phase, the expression of the mesenchymal proteins vimentin, neural cell adhesion molecules (Ncam), and the epithelial markers, Pax-2, Noggin, and basic fibroblast growth factor was observed; after, in a second phase, the tubular markers bone morphogen protein 7, Engrailed, and Lim-1, as well as the transcription factors Smad and p-Smad, were observed. Additionally, the endothelial markers VEGF and Tie-2 were induced at the initial and middle stages of regeneration phase, respectively. The expression of these proteins was restricted in time and space, as well as spatially and temporally. Because all of these proteins are important in maintaining a functional kidney, these results suggest that during the regeneration process after induced hypoxia, these nephrogenic proteins can be reexpressed in a similar fashion to that observed during development, thus restoring mature kidney function.
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PMID:Ischemic acute renal failure induces the expression of a wide range of nephrogenic proteins. 1628 88

Hippocampal kindling, a model of mesial temporal lobe epilepsy, is developed through repetitive stimulation of the hippocampus and leads to increased after-discharges as measured by EEG and an enduring seizure-prone state. Synthesis of new proteins is thought to form the basis for sustained seizure-induced physiological and/or pathological changes in synaptic reorganization and apoptotic/necrotic neuronal death. Here we examined the effect of kindling on stimulus-induced c-Jun N-terminal kinase (JNK) and p38 phosphorylation, events postulated to lie upstream of seizure-induced changes in gene transcription. We found that stimulus-induced phosphorylation of JNK, but not of p38, is significantly enhanced in kindled animals compared with their naive counterparts in the CA1 subregion of the hippocampus. Immunofluorescent staining confirmed this region-specific pattern of JNK activation and revealed that reactive astrocytes mediate this effect. Astrocyte proliferation and hypertrophy, as well as upregulation of vimentin protein levels, common markers of astrogliosis, were present after 4 d of kindling. Moreover, this reactive astrogliosis was associated with neuronal death as visualized with Fluoro-jade B and anti-active caspase-3 staining. Stimulus-induced phosphorylation of the JNK substrate paxillin was enhanced in kindled animals, but not that of c-Jun. Moreover, a pan-antibody against MAPK/CDK (mitogen-activated protein kinases/cyclin-dependent kinase) substrates indicated the presence of phosphorylated proteins in cytosolic, membrane, and nuclear fractions. The consequence of these phosphorylation events is not completely understood, but these findings suggest a selective astrocytic signaling response to aberrant synaptic activity, signaling that may modulate kindling progression and/or neuronal death.
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PMID:c-Jun N-terminal kinase activation responses induced by hippocampal kindling are mediated by reactive astrocytes. 1689 24

The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G2-M phase associated with the up-regulation of GADD45alpha-gamma and down-regulation of c-Myc. In treated cells, GADD45alpha-gamma and c-Myc were up- and down-regulated, respectively. A cascade of events leading to apoptotic mitochondrial 'intrinsic' pathway was observed in treated cells: (1) dephosphorylation of BAD serine136; (2) BAD dissociation from 14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4) caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor prevented the formation of cleavage products and, in turn, apoptosis was inhibited through a p53-independent mechanism. Moreover, these compounds did not activate NF-kappaB. Our findings may offer new insights into the mechanisms of action of these agents in A549 cells. The better understanding of their effects might be important to fully exploit the potential of these new drugs.
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PMID:Characterization of apoptosis induced by marine natural products in non small cell lung cancer A549 cells. 1700 27

An unusual type of hypertrophic astrocytes termed plump polygonal astrocytes (PPA) has been observed in the feline central nervous system which was characterized in a first preliminary study of 17 cats. These cells presented an oval to polygonal shape, measured about 20 microm in diameter, and displayed short, barely detectable processes. The condensed, hyperchromatic, eccentric nucleus was surrounded by an abundant, homogenous, eosinophilic cytoplasm. These GFAP-and S-100-positive and vimentin-negative cells were predominantly found in brains showing status spongiosus and less frequently in association with inflammation and in brains lacking histological lesions. They were mainly detected in white matter areas of the hindbrain. In addition, these cells were also observed in the dentate hilar region adjacent to degenerated neurons and a small amount of PPA were positive for caspase-3. It remains to be determined if PPA represent a specific type of reactive astrocytes and whether they are characteristic for a specific cause or response in the feline brain.
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PMID:Unusual type of reactive astrocytes in the feline central nervous system. 1748 98

Caspase-3 has classically been defined as the main executioner of programmed cell death. However, recent data supports the participation of this protease in non-apoptotic cellular events including cell proliferation, cell cycle regulation, and cellular differentiation. In this study, astroglial cleavage of caspase-3 was analyzed following excitotoxic damage in postnatal rats to determine if its presence is associated with apoptotic cell death, cell proliferation, or cytoskeletal remodeling. A well-characterized in vivo model of excitotoxicity was studied, where damage was induced by intracortical injection of N-methyl-D-asparate (NMDA) in postnatal day 9 rats. Our results demonstrate that cleaved caspase-3 was mainly observed in the nucleus of activated astrocytes in the lesioned hemisphere as early as 4 h postlesion and persisted until the glial scar was formed at 7-14 days, and it was not associated with TUNEL labeling. Caspase-3 enzymatic activity was detected at 10 h and 1 day postlesion in astrocytes, and co-localized with caspase-cleaved fragments of glial fibrillary acidic protein (CCP-GFAP). However, at longer survival times, when astroglial hypertrophy was observed, astroglial caspase-3 did not generally correlate with GFAP cleavage, but instead was associated with de novo expression of vimentin. Moreover, astroglial caspase-3 cleavage was not associated with BrdU incorporation. These results provide further evidence for a nontraditional role of caspases in cellular function that is independent of cell death and suggest that caspase activation is important for astroglial cytoskeleton remodeling following cellular injury.
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PMID:Caspase-3 activation in astrocytes following postnatal excitotoxic damage correlates with cytoskeletal remodeling but not with cell death or proliferation. 1748 78

Alcohol exposure during pregnancy may cause fetal alcohol syndrome (FAS), characterized by impaired cognitive functions. Neurogenesis occurs in the adult hippocampus and is functionally associated with learning, memory, and mood disorders. However, whether early postnatal exposure to alcohol impairs neurogenesis and through which mechanisms it occurs is poorly understood. Here, we report that a single episode of alcohol exposure in postnatal day 7 (P7) decreases neurogenesis in the adult hippocampus. Furthermore, we demonstrate a co-localization of glial fibrillar acidic protein, nestin, and vimentin with activated caspase-3 12 h after ethanol treatment. Finally, we show that the number of primary neurospheres derived from the hippocampi of alcohol-exposed mice is reduced compared to controls. These findings suggest that alcohol exposure in postnatal mice reduces the pool of neural stem/progenitor cells in the DG, and subsequently results in a decrease of adult neurogenesis. This may explain certain aspects of impaired hippocampal functions in FAS.
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PMID:Single alcohol exposure in early life damages hippocampal stem/progenitor cells and reduces adult neurogenesis. 1749 Aug 87

Our previous study has demonstrated that aloe-emodin induced a significant change in the expression of apoptosis-related proteins in H460 cells. However, the molecular mechanisms underlying the biological effects of aloe-emodin still remain unknown. The present study applied 2D electrophoresis (pH range 4-7) to the proteins involved in aloe-emodin (40 muM)-induced H460 cell apoptosis. Eleven proteins were found to markedly change. These altered proteins were identified as ATP synthase, vimentin, HSP60, HSP70 and protein disulfide isomerase. Aloe-emodin caused a time-dependent decrease in intracellular ATP levels, which might be related to direct inhibition of ATP synthase. We also observed that the activity of mitochondria was injured by aloe-emodin. These data clearly demonstrated that mitochondria may play a critical role in aloe-emodin-induced H460 cell death. Many reports emphasize that chaperones have a complex role in apoptosis. The present study suggested that the increasing protein expression of HSP60, HSP70, 150 kDa oxygen-regulated protein and protein disulfide isomerase is involved in aloe-emodin-induced H460 cell apoptosis. HSP70, 150 kDa oxygen-regulated protein and protein disulfide isomerase are endoplasmic reticulum chaperone. Therefore, we hypothesized that the increasing endoplasmic reticulum stress serves to promote H460 cell apoptosis after treatment with aloe-emodin. We also demonstrated aloe-emodin-induced H460 cell death through caspase-3 apoptotic pathway, but not apoptosis-inducing factor apoptotic pathway.
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PMID:Chaperones are the target in aloe-emodin-induced human lung nonsmall carcinoma H460 cell apoptosis. 1764 13

The role of the anti-cancer agent Viscum album agglutinin-I (VAA-I) in leukaemia PLB-985 cells differentiated toward a neutrophil-like phenotype by dimethylsulphoxide (PLB-985D) has never been studied. This study investigated whether or not VAA-I can induce cytoskeletal breakdown in PLB-985D cells, as previously observed in undifferentiated PLB-985 cells. VAA-I was found to induce apoptosis in PLB-985D cells, as assessed by cytology and by degradation of gelsolin, an event known to occur via caspase-3 activation. VAA-I induced cytoskeletal breakdown based on the disruption of the F-actin network and cleavage of paxillin, vimentin and lamin B(1). In addition, we demonstrated, for the first time, that non-muscle myosin heavy chain IIA (NMHC-IIA) was cleaved by VAA-I treatment. Degradation of NMHC-IIA was reversed by the pan caspase inhibitor z-VAD-fmk in PLB-985D cells and neutrophils. However, unlike lamin B(1), no NMHC-IIA was detected on the cell surface of apoptotic neutrophils. In conclusion, PLB-985D cells responded in a similar manner to neutrophils regarding the degradation of the tested cytoskeletal. Therefore, PLB-985D cells may provide a suitable substitute for neutrophils in screening experiments, preventing extensive neutrophil cell isolation.
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PMID:Viscum album agglutinin-I induces degradation of cytoskeletal proteins in leukaemia PLB-985 cells differentiated toward neutrophils: cleavage of non-muscle myosin heavy chain-IIA by caspases. 1765 56

Basal breast carcinomas triple negative for estrogen receptors, progesterone receptors and Her2/neu breast carcinomas are more aggressive than conventional neoplasms. We studied 64 cases with immunohistochemistry, using 23 antibodies, to characterize diverse pathological pathways. A basal cytokeratin was identified in 81% of tumors and vimentin was identified in 55%. The mean Ki67 index was 46% (range, 10-90%). Coincident expression of p50 and p65, which suggests an active nuclear factor-kappaB factor, was present in 13% of neoplasms. Epithelial growth factor receptor (EGFR), insulin-like growth factor-I receptor (IGF-IR) or c-kit (CD117) was identified in 77% of tumors. Loss of protein tyrosine phosphatase was found in 14%, whereas Akt activation was present in 28%. Several differences were identified between two subtypes of basal breast carcinomas: the pure variant (negative S-100 and actin) was more frequently associated with 'in situ carcinoma' (P=0.019) and pBad overexpression (P=0.098), whereas the myoepithelial variant (positive S-100 or actin) showed more frequent tumor necrosis (P=0.048), vimentin expression (P=0.0001), CD117 expression (P=0.001) and activated caspase-3 (P=0.089). IGF-IR could be as important as EGFR for the growth of these neoplasms. Basal cell carcinoma has at least two subtypes with distinct microscopic and immunohistochemical features.
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PMID:Immunohistochemical heterogeneity of breast carcinomas negative for estrogen receptors, progesterone receptors and Her2/neu (basal-like breast carcinomas). 1865 95

Aristolochic acid contamination in herbal remedies leads to interstitial fibrosis, tubular atrophy, and renal failure in humans. To study the cellular mechanisms contributing to the pathophysiology of this renal disease, we studied Wistar rats treated with aristolochic acid and measured tubular and interstitial cell proliferation, epithelial/mesenchymal cell marker expression, tubular membrane integrity, myofibroblast accumulation, oxidative stress, mitochondrial damage, tubular apoptosis, and fibrosis. Oxidative stress, a loss of cadherin concomitant with vimentin expression, basement membrane denudation with active caspase-3 expression, and mitochondrial injury within tubular cells were evident within 5 days of administration of the toxin. During the chronic phase, interstitial mesenchymal cells accumulated in areas of collagen deposits. Impaired regeneration and apoptosis of proximal tubular cells resulted in tubule atrophy with a near absence of dedifferentiated cell transmembrane migration. We suggest that resident fibroblast activation plays a critical role in the process of renal fibrosis during aristolochic acid toxicity.
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PMID:Aristolochic acid induces proximal tubule apoptosis and epithelial to mesenchymal transformation. 1809 81


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