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)

In view of the known involvement of oxidative stress and calcineurin (Ca(2+)-calmodulin dependent protein phosphatase) in beta-Adrenergic stimulated events, we examined the influence of eugenol (an antioxidant generally regarded as safe by the Food and Agricultural Organization of the United Nations) on isoproterenol-induced apoptosis in neonatal cardiomyocytes. In comparison to unstimulated controls, cardiomyocytes stimulated with 50 microM isoproterenol for 48 h demonstrated (a) increased intracellular Ca(2+) levels (b) oxidative stress involving enhanced reactive oxygen species, decreased GSH/GSSG ratio, enhanced lipid peroxidation, increased activities of superoxide dismutase and glutathione peroxidase (c) apoptosis, evidenced by increased number of annexin V/TUNEL positive cells, enhanced membrane fluidity, decreased mitochondrial membrane potential, increased activities of caspase 3 and 9 along with (d) increased calcineurin activity. Pre-incubation of cardiomyocytes with 100 microM eugenol for 1 h, followed by isoproterenol treatment for 48 h, led to reversal of enhanced intracellular Ca(2+) levels, oxidative stress, calcineurin activation and apoptosis caused by isoproterenol. In addition, similar treatment of cardiomyocytes with 10 nM FK506, a calcineurin inhibitor, could also attenuate isoproterenol-induced apoptosis. These results indicate the beneficial effects of eugenol in preventing cardiomyocyte apoptosis.
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PMID:Interrelations between oxidative stress and calcineurin in the attenuation of cardiac apoptosis by eugenol. 1644 93

Steatohepatitis has recently been increasing as a cofactor influencing the progression of fibrosis, cirrhosis, adenoma and carcinoma in liver; however, the mechanisms by which it contributes to liver injury remain uncertain. We induced steatohepatitis in zebrafish embryos using thioacetamide (TAA). TUNEL assay revealed significant increasing of apoptosis in liver after 5 days post fertilization and the increasing of apoptosis was observed to be associated with the up-regulation of apoptotic genes such as, bad, bax, P-38a, caspase-3 and 8, and JNK-1. Histological sections by oil red O stain showed the accumulation of fatty droplets which causes the pushing of the nucleus towards one side. Up-regulation of steatosis markers such as, ACC, adiponectin, PTL, CEBP- alpha and beta, SREBP-1 was also observed. Furthermore, the elevation of glutathione peroxidase in TAA treated embryos indicated that TAA induces lipid peroxidation which leads to causes liver damage. Zebrafish has already been considered as a good human disease model and in this context; TAA-treated zebrafish may serve as a good animal model to study the molecular pathogenesis of steatohepatitis. Moreover, non-availability of specific drugs to prevent steatohepatitis, this animal model may serve as a powerful preclinical platform to study the therapeutic strategies and for evaluating chemoprevention strategies for this disease.
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PMID:Thioacetamide induced liver damage in zebrafish embryo as a disease model for steatohepatitis. 1645 12

Chronic systemic exposure of D-galactose to mice, rats, and Drosophila causes the acceleration of senescence and has been used as an aging model. However, the underlying mechanism is as yet unclear. To investigate the mechanisms of neurodegeneration in this model, we studied cognitive function, hippocampal neuronal apoptosis and neurogenesis, and peripheral oxidative stress biomarkers and also the protective effects of the antioxidant R-alpha-lipoic acid. Chronic systemic exposure of mice to D-galactose (100 mg/kg, s.c., 7 weeks) induced a spatial memory deficit, an increase in cell karyopyknosis, apoptosis, and caspase-3 protein levels in hippocampal neurons, a decrease in the number of new neurons in the subgranular zone in the dentate gyrus, a reduction of migration of neural progenitor cells, and an increase in death of newly formed neurons in the granular cell layer. The D-galactose exposure also induced an increase in peripheral oxidative stress, including an increase in malondialdehyde and decreases in total antioxidative capabilities (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) activities. A concomitant treatment with lipoic acid ameliorated cognitive dysfunction and neurodegeneration in the hippocampus and also reduced peripheral oxidative damage by decreasing malondialdehyde and increasing T-AOC and T-SOD, without an effect on GSH-Px. These findings suggest that chronic D-galactose exposure induces neurodegeneration by enhancing caspase-mediated apoptosis and inhibiting neurogenesis and neuron migration, as well as increasing oxidative damage. In addition, D-galactose-induced toxicity in mice is a useful model for studying the mechanisms of neurodegeneration and neuroprotective drugs and agents.
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PMID:Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-alpha-lipoic acid. 1655 1

Cholinergic and gabaergic systems play an important role generating electroencephalographic activity and regulating vigilance states. Pilocarpine is a cholinergic agonist commonly used to induce seizures and an epilepticus-like state in rodents. A relationship between status epilepticus and reactive oxygen species has been also suggested which could result in seizure-induced neurodegeneration. The aim of this study was to evaluate the existence of oxidative damage as well as the antioxidant enzyme response in cortex and hippocampus after the administration of an intraperitoneal (350 mg/kg) and an intracerebroventricular (360 microg, 1 microl) pilocarpine injection in rats. The GABA agonist muscimol (1 mg/kg, i.p.), with described neuroprotective properties, was used as a negative control. Only systemic pilocarpine induced oxidative damage. Malondialdehyde levels, as a marker of lipid peroxidation (LP), increased in both regions (55-56%). Catalase (52-80%) and superoxide dismutase (53-60%) activities also rose in both regions but glutathione peroxidase activity only increased in cortex (45%). Glutathione reductase and caspase-3 activity did not change. In conclusion, systemic pilocarpine produced oxidative brain damage, whereas local pilocarpine brain injection had no effects. Moreover, the enzymatic determinations performed in this study are a good tool to study brain injury in pharmacological manipulations such as the ones used in short recording EEG studies.
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PMID:Antioxidant response analysis in the brain after pilocarpine treatments. 1664 87

Chronic systemic exposure of mice, rats, and Drosophila to D-galactose causes the acceleration of senescence and has been used as an aging model. The underlying mechanism is yet unclear. To investigate the mechanisms of neurodegeneration in this model, we studied cognitive function, hippocampal neuronal apoptosis and neurogenesis, and peripheral oxidative stress biomarkers, and also the protective effects of the antioxidant R-alpha-lipoic acid. Chronic systemic exposure of D-galactose (100 mg/kg, s.c., 7 weeks) to mice induced a spatial memory deficit, an increase in cell karyopyknosis, apoptosis and caspase-3 protein levels in hippocampal neurons, a decrease in the number of new neurons in the subgranular zone in the dentate gyrus, a reduction of migration of neural progenitor cells, and an increase in death of newly formed neurons in granular cell layer. The D-galactose exposure also induced an increase in peripheral oxidative stress, including an increase in malondialdehyde, a decrease in total anti-oxidative capabilities (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) activities. A concomitant treatment with lipoic acid ameliorated cognitive dysfunction and neurodegeneration in the hippocampus, and also reduced peripheral oxidative damage by decreasing malondialdehyde and increasing T-AOC and T-SOD, without an effect on GSH-Px. These findings suggest that chronic D-galactose exposure induces neurodegeneration by enhancing caspase-mediated apoptosis and inhibiting neurogenesis and neuron migration, as well as increasing oxidative damage. In addition, D-galactose-induced toxicity in mice is a useful model for studying the mechanisms of neurodegeneration and neuroprotective drugs and agents.
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PMID:Chronic systemic D-galactose exposure induces memory loss, neurodegeneration, and oxidative damage in mice: protective effects of R-alpha-lipoic acid. 1671 Aug 48

Radix Angelica sinensis, known as Danggui in Chinese, has been used to treat cardiovascular and cerebrovascular diseases in Traditional Chinese Medicine for a long time. Modern phytochemical studies showed that Z-ligustilide (LIG) is the main lipophilic component of Danggui. In this study, we examined whether LIG could protect ischemia/reperfusion-induced brain injury by minimizing oxidative stress and anti-apoptosis. Transient forebrain cerebral ischemia (FCI) was induced by the bilateral common carotid arteries occlusion for 30 min. LIG was intraperitoneally injected to ICR mice at the beginning of reperfusion. As determined via 2,3,5-triphenyl tetrazolium chloride (TTC) staining at 24 h following ischemia, the infarction volume in the FCI mice treated without LIG (22.1 +/- 2.6%) was significantly higher than that in the FCI mice treated with 5 mg/kg (11.8 +/- 5.2%) and 20 mg/kg (2.60 +/- 1.5%) LIG (P < 0.05 or P < 0.01). LIG treatment significantly decreased the level of malondialdehyde (MDA) and increased the activities of the antioxidant enzyme glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) in the ischemic brain tissues (P < 0.05 or P < 0.01 vs. FCI group). In addition, LIG provided a great increase in Bcl-2 expression as well as a significant decrease in Bax and caspase-3 immunoreactivities in the ischemic cortex. The findings demonstrated that LIG could significantly protect the brain from damage induced by transient forebrain cerebral ischemia. The antioxidant and anti-apoptotic properties of LIG may contribute to the neuroprotective potential of LIG in cerebral ischemic damage.
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PMID:Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice. 1680 12

Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induces apoptosis of glioma cells in vitro and tumor regression in vivo. The present study investigated a possible involvement of caspase activation and reactive oxygen species (ROS) induction in the apoptotic effect of CBD. CBD produced a gradual, time-dependent activation of caspase-3, which preceded the appearance of apoptotic death. In addiction, release of cytochrome c and caspase-9 and caspase-8 activation were detected. The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione and increase activity of glutathione reductase and glutathione peroxidase enzymes. Under the same experimental condition, CBD did not impair primary glia. Thus, we found a different sensitivity to the anti-proliferative effect of CBD in human glioma cells and non-transformed cells that appears closely related to a selective ability of CBD in inducing ROS production and caspase activation in tumor cells.
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PMID:The non-psychoactive cannabidiol triggers caspase activation and oxidative stress in human glioma cells. 1690 7

Clinical observations suggest that certain gut and dietary factors may transiently worsen symptoms in autism spectrum disorders (ASD), epilepsy and some inheritable metabolic disorders. Propionic acid (PPA) is a short chain fatty acid and an important intermediate of cellular metabolism. PPA is also a by-product of a subpopulation of human gut enterobacteria and is a common food preservative. We examined the behavioural, electrophysiological, neuropathological, and biochemical effects of treatment with PPA and related compounds in adult rats. Intraventricular infusions of PPA produced reversible repetitive dystonic behaviours, hyperactivity, turning behaviour, retropulsion, caudate spiking, and the progressive development of limbic kindled seizures, suggesting that this compound has central effects. Biochemical analyses of brain homogenates from PPA treated rats showed an increase in oxidative stress markers (e.g., lipid peroxidation and protein carbonylation) and glutathione S-transferase activity coupled with a decrease in glutathione and glutathione peroxidase activity. Neurohistological examinations of hippocampus and adjacent white matter (external capsule) of PPA treated rats revealed increased reactive astrogliosis (GFAP immunoreactivity) and activated microglia (CD68 immunoreactivity) suggestive of a neuroinflammatory process. This was coupled with a lack of cytotoxicity (cell counts, cleaved caspase 3' immunoreactivity), and an increase in phosphorylated CREB immunoreactivity. We propose that some types of autism may be partial forms of genetically inherited or acquired disorders involving altered PPA metabolism. Thus, intraventricular administration of PPA in rats may provide a means to model some aspects of human ASD in rats.
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PMID:Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. 1695 May 24

We previously showed that long-term exposure of anterior pituitary cells to nitric oxide (NO) induces apoptosis. The intracellular signals underlying this effect remained unclear. In this study, we searched for possible mechanisms involved in the early stages of the NO apoptotic cascade. Caspase 3 was activated by NO with no apparent disruption of mitochondrial membrane potential. NO caused a rapid increase of reactive oxygen species (ROS), and this increase seems to be dependent of mitochondrial electron transport chain. The antioxidant N-acetyl-cysteine avoided ROS increase, prevented the NO-induced caspase 3 activation, and reduced the NO apoptotic effect. Catalase was inactivated by NO, while glutathione peroxidase (GPx) activity and reduced glutathione (GSH) were not modified at first, but increased at later times of NO exposure. The increase of GSH level is important for the scavenging of the NO-induced ROS overproduction. Our results indicate that ROS have an essential role as a trigger of the NO apoptotic cascade in anterior pituitary cells. The permanent inhibition of catalase may strengthen the oxidative damage induced by NO. GPx activity and GSH level augment in response to the oxidative damage, though this increase seems not to be enough to rescue the cells from the NO effect.
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PMID:Reactive oxygen species are key mediators of the nitric oxide apoptotic pathway in anterior pituitary cells. 1699 55

There is increasing evidence showing dual functions of antioxidant enzymes in coping with reactive oxygen species (ROS) versus reactive nitrogen species (RNS). The objective of this study was to compare the impacts of knockout of Cu, Zn-superoxide dismutase (SOD1) and Se-dependent glutathione peroxidase-1 (GPX1) on cell death and related signaling mediated by acetaminophen (APAP), a RNS inducer in liver. Two groups of young adult knockout mice (SOD1(-/-) and GPX1(-/-)), along with their wild types (WT), were killed 5 hrs after an ip injection of saline or APAP (300 mg/kg body wt). While the WT mice showed more hepatic necrosis and DNA breakage than the GPX1(-/-) mice, the SOD1(-/-) mice had essentially no positive response compared with their saline-injected controls. The APAP treatment activated liver c-jun N-terminal kinase (JNK) in the WT and GPX1(-/-) mice, but not in the SOD1(-/-) mice. The APAP-induced changes in other cell death-related signal proteins such as p21, caspase-3, and poly(ADP-ribose) polymerase (PARP) also were obviated in the SOD1(-/-) mice. In conclusion, knockout of GPX1 did not potentiate APAP-induced cell death and related signaling, whereas the SOD1 null blocked APAP-induced hepatic JNK phosphorylation and cell death.
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PMID:Impact of Cu, Zn-superoxide dismutase and Se-dependent glutathione peroxidase-1 knockouts on acetaminophen-induced cell death and related signaling in murine liver. 1713 59


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