Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male Wistar rats were subjected to intraperitoneal (i.p.) streptozotocin (STZ) administration (85 mg/kg) to evoke diabetes. Cerebral ischaemia was produced by injection of 0.03 ml of air into the left carotid followed by bilateral common carotid ligation. We studied the effect of application of two antioxidants--coenzyme Q10 (CoQ10, 10 mg/kg b.w., i.p. for seven days) and lipoic acid (LA, 100 mg/kg b.w., i.p. for seven days) on neurones and on the apoptosis-related enzyme--caspase-3 activity in the hippocampus and dentate gyrus. Ischaemia and diabetes lead to a decrease of nuclear and perikaryon diameters as well as neuronal density in the CA1, CA2, CA3 and dentate gyrus. Application of CoQ10 or LA for seven days improved the mean nucleus area and perikaryon area in almost all investigated structures. Both antioxidants diminished neuronal loss in the diabetes complicated with ischaemia but not in the animals with diabetes only. Activity of one of the key enzymes in apoptotic cell death, caspase-3 (CPP32), increased in hippocampus in the diabetic rats, in the animals with cerebral ischaemia and in the rats with both diabetes and ischaemia by about 80%, 33% and 53%, respectively. Either the CoQ10 or the LA treatment led to a significant decrease of the CPP32 activity in all experimental groups. Our results confirm the presence of neuronal damage and death in the hippocampus and dentate gyrus in the experimental STZ-diabetes and its aggravation by the additional cerebral ischaemia. The effects of the antioxidative treatment support the hypothesis of an important role of oxidative stress and free radicals in neuronal pathology in diabetes and ischaemia. The above results of CPP32 activity suggest an important role of apoptosis as a mechanism of cell death and demonstrate the positive effect of the CoQ10 and the LA treatment.
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PMID:Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischaemia treated with antioxidants. 1177 Jan 25

During pregnancy, infection or immune responses induce cytokine release, which might influence fetal neurodevelopment, leading to neurodegenerative disease in adulthood. Because the hippocampus is a key area for learning and memory, we evaluated 4- and 24-wk-old rats for the effects of early and late prenatal exposure to interleukin-6 (IL-6) on hippocampal morphology, expression of mRNA for IL-6, the gamma-aminobutyric acid receptor (GABA(Aalpha5)), the NR1 subunit of the N-methyl-D-aspartate receptor, and glial fibrillary acidic protein (GFAP), caspase-3 protein and mRNA levels, and learning abilities. Late exposure increased serum IL-6 and hippocampal expression of IL-6 mRNA at 4 and 24 wk. All adult rats showed neuronal loss in the hilus and astrogliosis; males had losses mainly in the CA2 and CA3 regions, and females in CA1. Expression of GABA(Aalpha5), NR1, and GFAP mRNA increased in late-exposed males and females at 4 and 24 wk. mRNA and protein levels of the apoptosis marker caspase-3 were increased in all late-exposed rats except males at 4 wk. Evaluation of hippocampus-dependent working memory in the Morris water maze at 20 wk of age showed increases in escape latency and time spent near the pool wall in all IL-6 adult rats, especially females. These findings suggest that fetal IL-6 exposure, especially in late pregnancy, leads to increased IL-6 levels in the circulation and hippocampus, abnormalities of hippocampal structural and morphology, and decreased learning during adulthood.
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PMID:Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning. 1635

Increasing evidence suggests that apoptosis is a contributing factor to neuronal cell death in traumatic brain injury (TBI). There is increased expression, cleavage and activation of caspases as well as other proteins known to regulate apoptosis in neurons after TBI. These proteins include the proto-oncogene Bcl-2 which belongs to a family of proteins with both pro- and anti-apoptotic properties. To investigate the role of apoptosis in TBI and the importance of Bcl-2 protein on the severity and outcome of injury, Bcl-2 overexpressing transgenic and wild-type control mice were subjected to the controlled cortical impact model of TBI. There was no significant difference in the cleavage of caspase-3 or caspase-9 detected by Western blotting of hippocampal samples from transgenic or wild-type mice after TBI. Bcl-2 transgenic mice had smaller contusion volumes and increased numbers of surviving neurons in CA2 but not other regions of hippocampus compared to wild-type controls. By contrast, there was no difference in motor function determined by the round beam balance and wire grip tests between transgenic and wild-type mice after TBI. Cognitive function assessed by the Morris water maze was also not different between groups. These results suggest that overexpression of Bcl-2 is only partially neuroprotective and other members of this protein family may prove to be more important in protecting neurons from cell death.
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PMID:Transgenic mice that overexpress the anti-apoptotic Bcl-2 protein have improved histological outcome but unchanged behavioral outcome after traumatic brain injury. 1678 76

It has been shown that cytochrome-c-dependent caspase-3 activation is significantly elevated in the aging macaque brain. To assess the underlying age-related changes in the cellular distribution of caspase-3, we have examined the motor cortex, cerebellum and hippocampus of young (4-year-old, n = 4) and old (20-year-old, n = 4)rhesus monkeys by immunohistochemistry. Western blot analyses of brain homogenate showed that the antibody reacted only with inactive 32-kDa procaspase and its active 20- and 17-kDa subunits, formed after granzyme B exposure. In the motor cortex, pyramidal cells of layers III and V were moderately labeled; the underlying white matter contained weakly stained astrocytes. In the hippocampus, hilar neurons and pyramidal cells in CA3 showed the strongest immunoreaction, pyramidal cells in CA1 and granule cells of the dentate gyrus were also strongly labeled. In contrast, CA2 pyramidal cells were only weakly stained, and neurons of the molecular layer were unlabeled. Weak caspase-3 immunoreaction of CA2 neurons parallels known decreased susceptibility to apoptosis. In the cerebellar cortex, clusters of strongly labeled Purkinje cells were observed next to groups of weakly and unstained cells; granule cells were generally unstained. The brains of aging monkeys displayed a similar pattern of caspase-3 immunoreactivity. In neocortical layer V, however, scattered very strongly labeled pyramidal cells were regularly detected, which were not observed in younger animals. This clustering of caspase-3 indicates increased vulnerability of a subset of pyramidal cells in the aging brain.
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PMID:Caspase-3 immunoreactivity in different cortical areas of young and aging macaque (Macaca mulatta) monkeys. 1684 99

Neonatal hypoxia-ischemia (HI) induces immediate early gene (IEG) c-fos expression as well as neuron death. The precise role of IEGs in neonatal HI is unclear. We investigated the temporal and spatial patterns of c-Fos expression in postnatal day 7 mice after unilateral carotid ligation and exposure to 8% oxygen. mRNA levels of c-fos quantitated by real-time polymerase chain reaction (PCR) increased nearly 40-fold (log 1.2 +/- 0.4) in the ipsilateral hippocampus 3 hr following neonatal HI, then returned to basal levels within 12 hr, although no change was observed in c-jun mRNA. Frozen coronal brain sections were stained with cresyl violet or used for immunohistochemical detection of c-Fos, cleaved caspase-3, glial fibrillary acidic protein (GFAP), and the mature neuron marker NeuN. c-Fos immunoreactivity increased throughout the injured hippocampus 3 hr after HI but became restricted to the CA2-3 subregion and the dentate gyrus (DG) at 6-12 hr and declined by 24 hr. In contrast, cleaved (activated) caspase-3 immunoreactivity was most abundant in the ipsilateral CA1 region at 3-6 hr after neonatal HI, then became more prominent in CA2-3 and DG. Double-labeling experiments showed c-Fos and cleaved caspase-3 immunoreactivity localized in spatially distinct neuron subpopulations. Prominent c-Fos immunoreactivity was observed in surviving CA2-3 and external granular DG neurons, and robust cleaved caspase-3 immunoreactivity was observed in pyknotic CA1, CA2-3, and subgranular DG neurons. The differential expression of c-Fos in HI-resistant hippocampal subpopulations vs. cleaved caspase-3 in dying neurons suggests a neuroprotective role for c-Fos expression in neonatal HI.
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PMID:Differential activation of c-fos and caspase-3 in hippocampal neuron subpopulations following neonatal hypoxia-ischemia. 1803 Jun 77

Transient occlusion of common carotid arteries in gerbils is a simple and widely used model for assessing histological and functional consequences of transient forebrain ischemia and neuroprotective action of pharmaceuticals. In the present study we aimed to introduce additional behavioural tests as novel object recognition and food-motivated hole-board learning in order to measure attention and learning capacity in gerbils. For validating these cognitive tests the effects of ageing (4, 9 and 18 months) and those of transient forebrain ischemia induced by bilateral carotid occlusion at 9 months of age were investigated. Neuronal cell death was estimated in the hippocampus using TUNEL and caspase-3 double fluorescence labelling and confocal microscopy. Ageing within the selected range although influenced ambulatory activity, did not considerably change attention and memory functions of gerbils. As a result of transient ischemia a selective neuronal damage in CA1 and CA2 regions of the hippocampus has been observed and tested 4 days after the insult. Ischemic gerbils became hyperactive, but showed decreased attention and impaired spatial memory functions as compared to sham-operated controls. According to our results the novel object recognition paradigm and the hole-board spatial learning test could reliably be added to the battery of conventional behavioural tests applied previously in this species. The novel tests can be performed within a wide interval of adult age and provide useful additional methods for assessing ischemia-induced cognitive impairment in gerbils.
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PMID:Adopted cognitive tests for gerbils: validation by studying ageing and ischemia. 1922 5

The hippocampal fields of neonatal rats differ by the level of active caspase-3: dentate gyrus >CA3>CA1>CA2. In the dentate gyrus it was 70% of its maximum value in the cortex, while in CA2 it corresponded to the minimum level in the brain stem. Taking into account the role of caspase-3 in apoptosis, these differences can indicate different intensity of programmed cell death in different fields of the forming hippocampus.
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PMID:Immunohistochemical analysis of active caspase-3 expression in structures of neonatal brain. 1990 58

There is a huge body of evidence showing that long-termed diabetes mellitus is followed with hippocampal dysfunction. The goal of this work was to investigate the expression of proteasome subunits PSMB5 and PSMB9 mRNA in CA1, CA2 and CA3 areas of hippocampus in parallel with processes of cell death (apoptosis and necrosis) in development dynamics of streptozotocine-induced diabetes. We have studied hippocampal neurons using chromatine dye Hoechst-33342 and immunohistochemical detection of apoptotic cell death marker caspase-3. At day 3 and 7 after injection of streptozotocine we have performed visualization of caspase-3-immunopositive neurons showing signs of neurodegeneration in hippocampal sections using confocal microscope Olympus FV1000. The rate of proteasome subunits PSMB5 and PSMB9 mRNA expression was determined with RT-PCR. The results indicated elevation of PSMB9 mRNA content (from 4807 +/- 0.392 arbU up to 20,023 +/- 4949 arbU on day 3 and up to 20,253 +/- 5141 arbU on day 7). A maximal number of cells with signs of chromatin condensation was observed at day 3 and day 7 in CA2 and CA3 area (11.51% and 12.49% respectively). That indicates an intensification of proapoptotic processes. Summarizing the results presented above we can conclude that during the first week of diabetes mellitus development, hippocampal cells undergo the process of impairment and degeneration.
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PMID:[Expression of proteasome subunits PSMB5 and PSMB9 mRNA in hippocampal neurons in experimental diabetes mellitus: link with apoptosis and necrosis]. 2096 39

To identify quantitative MRI indices of injury in the brain following neonatal hypoxic-ischemic brain injury, we subjected mouse pups to hypoxia-ischemia on postnatal day 7 and obtained conventional and diffusion-weighted in vivo images of the brain 24 h later followed by histological assessment. T(2)-weighted images showed increased signal intensity in the CA1 and CA2 regions of the hippocampus ipsilateral to the injury and adjacent white matter. In contrast, diffusion imaging showed reduced apparent diffusion coefficient (ADC) values in CA1 and CA2, but increased values in the adjacent white matter. Histological analysis showed widespread gliosis with degenerating oligodendrocytes in the ipsilateral hippocampus. In addition, white matter areas that were abnormal by MRI showed an increase in the number of activated microglia (CD45 positive cells). Activated caspase-3 immunostaining showed a marked increase in neurons in the hippocampal regions corresponding to those with reduced ADC, and a quantitative measure of staining showed a statistically significant correlation with the ADC. In contrast, ADC was higher in adjacent white matter, where histology showed activation of microglia and reactive oligodendrocytes but not caspase-3 activation. These results suggest that the ADC response differs between areas of neuronal injury as compared with those showing glial changes without marked cell death.
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PMID:Diffusion characteristics associated with neuronal injury and glial activation following hypoxia-ischemia in the immature brain. 2139 76

Anabolic-androgenic steroids (AAS) are used in the medical treatment of many disorders. Erythropoietin (EPO) is a hematopoietic cytokine that has anti-apoptotic, anti-oxidative, and anti-inflammatory effects. The aim of the present study is to investigate the neuroprotective effects of EPO in the hippocampus, parietal cortex and prefrontal cortex, in brain damage due to nandrolone decanoate. 35 Wistar male rats were randomly divided into: (1) control group, (2) sham group, (3) nandrolone decanoate group (ND, intramuscular, 10 mg/(kg week), 8 weeks), (4) ND+low dose EPO treated group (ND+L-EPO) and (5) ND+high dose EPO treated group (ND+H-EPO). EPO was administrated by intraperitoneal injection at a dose of 100 U/(kg day) for L-EPO treatment and at a dose of 500 U/(kg day) for H-EPO treatment during 8 weeks. The number of neurons of CA1, CA2, CA3 and dentate gyrus of hippocampus, parietal cortex and prefrontal cortex were significantly less in the ND group compared with the control group. Treatment with H-EPO significantly preserved the number of neurons in hippocampus when compared with ND administrated. Besides, H-EPO treatment decreased the number of TUNEL-positive and active caspase-3 positive cells and MDA levels and increased GPx levels when compared to ND group. In conclusion, abuse of AAS causes reduction in the number of neurons in hippocampus, parietal cortex and prefrontal cortex regions and increases oxidative damage and therefore H-EPO may be useful as a neuroprotective agent in brain injury.
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PMID:Neuroprotective effect of erythropoietin on nandrolone decanoate-induced brain injury in rats. 2306 52


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