Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inadequate oxygen availability at high altitude causes oxidative stress and generation of reactive oxygen species, which may lead to memory impairment. Hippocampus, which plays a key role in the learning and memory processes, is especially vulnerable to hypoxic damage. The present study was aimed at investigating the effect of acetyl-L-carnitine on spatial working and reference memory deficits along with oxidative and apoptotic damage, caused by hypobaric hypoxia in male Sprague Dawley rats. Rats were trained in Morris Water Maze for eight days after which they were submitted to chronic hypobaric hypoxia exposure at a simulated altitude of 6100 m for three days. Rats received daily acetyl-L-carnitine at a dosage of 75 mg/kg body weight orally during exposure. Subsequent to exposure, performance of the animals was tested in Morris Water Maze, which revealed working memory impairment that was significantly improved by acetyl-L-carnitine. However, there was no change in the reference memory after hypobaric hypoxia exposure. Following behavioral study animals were sacrificed and biomarkers of oxidative damage like free radical production, lactate dehydrogenase activity, lipid peroxidation, antioxidant status and expression of apoptotic [viz. caspase-3, Apoptosis activating factor (Apaf-1), bax, cytochrome c] and anti-apoptotic protein-Bcl-2 were studied in the hippocampus. There was a significant increase in oxidative stress along with increased expression of apoptotic proteins and NR1 subunit of glutamate receptor indicating occurrence of excitotoxicity in hypoxia exposed rats. These results suggested that supplementation with acetyl-L-carnitine improves spatial working memory deficits reduces oxidative stress and inhibits apoptotic cascade induced by hypoxia.
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PMID:Acetyl-L-carnitine ameliorates hypobaric hypoxic impairment and spatial memory deficits in rats. 1761 Aug 72

We examined the effect of daily melatonin supplementation on liver apoptosis induced by aging in rats. Young (3-month-old) and aged (24-month-old) Wistar rats were supplemented daily with melatonin in their drinking water (20 mg/L) for 4 weeks. Aged rats showed increases in the liver concentration of thiobarbituric acid-reactive substances and in the oxidized/reduced glutathione ratio. These increases were accompanied by apoptotic ultrastructural alterations and increases in cytochrome c mitochondrial release, Bax to Bcl-2 relative expression, and activity of caspase-3. No significant changes were observed in Fas-ligand (Fas-L) expression and caspase-8 activity. Melatonin administration was able to abrogate changes detected in aged rats. Data suggest that liver apoptotic cell death is induced by reactive oxygen species, via the intrinsic signalling pathway, and that the antiapoptotic action provided by melatonin is related to its antioxidant effect, with reduction of cytochrome c release by the modulation of Bcl-2 and Bax genes.
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PMID:Melatonin is able to reduce the apoptotic liver changes induced by aging via inhibition of the intrinsic pathway of apoptosis. 1763 14

Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na(+)-K(+)-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-alpha)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na(+)-K(+)-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF(2alpha), and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension.
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PMID:Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat. 1765 67

Moderate hyperhomocysteinemia is a risk factor for neurodegenerative diseases and complications during pregnancy. Increased homocysteine levels during pregnancy may elevate developmental risk on fetal brain structure and function. However, little is known about the mechanism of action of homocysteine on the degeneration of the fetal brain. Hence in this study, we examined the effects of maternal hyperhomocysteinemia on oxidative stress and apoptosis in brain tissues and investigated whether administration of melatonin to the mother would prevent homocysteine-induced oxidative cerebral damage in pups. Hyperhomocysteinemia was induced in female rats by administration of methionine at a dose of 1 g/kg body weight dissolved in drinking water during pregnancy. Some animals received methionine plus 10 mg/kg/day melatonin subcutaneously throughout pregnancy. After delivery, the level of lipid peroxidation (malondialdehyde + 4-hydroxyalkenals) was determined in different subfractions of pup brains. Furthermore, DNA fragmentation, levels of Bcl-2 protein and p53 mRNA expression were determined to evaluate apoptosis. Significant elevation was found in the levels of lipid peroxidation in subcellular fractions of the brain of pups of hyperhomocysteinemic dams. Increased DNA fragmentation and p53 mRNA expression was observed in the brain of pups of homocysteine-treated rats, while a significant reduction was seen in the levels of anti-apoptotic Bcl-2 levels. Melatonin administration prevented markers of oxidative stress and biochemical signs of apoptosis. In conclusion, therapeutic administration of melatonin protects against the induction of oxidative stress and neural tissue injury and might prevent congenital malformations of fetal brain caused by maternal hyperhomocysteinemia.
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PMID:Melatonin inhibits oxidative stress and apoptosis in fetal brains of hyperhomocysteinemic rat dams. 1780 18

In the present study, we assessed whether concurrent treatment with low doses of cilostazol and donepezil effectively improve memory deficits in association with amelioration of the pathological changes in the white matter of rats subjected to permanent ligation of bilateral common carotid arteries (BCCAL). The escape latency in Morris water maze test was significantly increased at 7, 14 and 21 days in rats subjected to BCCAL. At 21 days after ligation, the white matter lesions including vacuole formation with rarefaction were increased in the optic tract and corpus callosum accompanied by a large increase in glial fibrillary acidic protein (GFAP) immunoreactivity with significantly decreased CNPase-positive oligodendrocytes, all of which were significantly alleviated by the combination therapy with suboptimal doses of cilostazol (30 mg/kg orally) and donepezil (0.3 mg/kg intraperitoneally). The phosphorylated cyclic AMP response element-binding protein (p-CREB)- and Bcl-2-positive cells were significantly decreased following BCCAL, which were completely restored by the combination therapy, whereas the monotherapy with cilostazol or donepezil showed marginal effect. In conclusion, concurrent treatment with cilostazol and donepezil effectively prevented the occurrence of neuropathological alterations in the white matter by activation of p-CREB and Bcl-2, thereby resulting in improvement of spatial learning memory in rats subjected to chronic cerebral hypoperfusion.
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PMID:Concurrent administration of cilostazol with donepezil effectively improves cognitive dysfunction with increased neuroprotection after chronic cerebral hypoperfusion in rats. 1793 28

Lead is a neurotoxin that affects the developing central nervous system and may potentially induce apoptotic cell death. We investigated the effect of ascorbic acid against lead-induced neurotoxicity in the developing rat hippocampus. Female Sprague-Dawley rats were divided into three groups: control group, lead-treated group and lead plus ascorbic acid-treated group. Lead (0.2% lead acetate) was administered to female rats during pregnancy and lactation, in their drinking water. During this period, rats in the lead plus ascorbic acid-treated group received 100 mg/kg/day ascorbic acid, orally. At the end of the treatment, neuronal damage, apoptosis and blood lead levels were determined and the levels of Bax and Bcl-2 were immunodetected in the hippocampus of 21-day-old male pups. Histopathological evaluation demonstrated that ascorbic acid significantly attenuates apoptosis in the developing hippocampus and also spares hippocampal CA1, CA3 and dentate gyrus (DG) neurons. Simultaneous administration of ascorbic acid and lead lowered the level of Bax protein and increased Bcl-2 in pup hippocampus and reduced lead level in blood of dams compared with lead-treated only. Based on these results, it seems that ascorbic acid may potentially be beneficial in treating lead-induced brain injury in the developing rat brain.
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PMID:Protective effects of ascorbic acid against lead-induced apoptotic neurodegeneration in the developing rat hippocampus in vivo. 1795 57

The aim of the present study was to access the protective effect of a novel synthesized squamosamide cyclic analogue, compound FLZ, on memory impairment in artificially senescent mice induced by chronic injection of D-galactose and sodium nitrite (NaNO(2)). Artificially senescent mouse model was induced by consecutive injection of D-galactose (120 mg/kg) and NaNO(2) (90 mg/kg) once daily for 60 days. Compound FLZ (75 and 150 mg/kg) was orally administered once daily for 30 days after D-galactose and NaNO(2) injection for 30 days. The water maze test was used to evaluate the learning and memory function of mice. The content of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in serum were determined using different biochemical kits. The alterations in hippocampus morphology were assessed by light and electronic microscope. Immunoreactive cells of Bcl-2 in the hippocampus were counted by immunohistochemical staining, and Bcl-2 protein expression was analysed by Western blot method. The results indicate that injection of D-galactose and NaNO(2) induces memory impairment and neuronal damage in hippocampus of mice. In addition, serum SOD and GSH-Px activities decreased, while MDA level increased. Bcl-2-positive neurons and Bcl-2 protein expression in the hippocampus decreased remarkably. Oral administration of FLZ for 30 days significantly improved the cognitive deficits and the biochemical markers mentioned above, and also reduced the pathological alterations in mouse hippocampus. The results suggest that FLZ ameliorates memory deficits and pathological injury in artificially senescent mice induced by chronic injection of D-galactose and NaNO(2), indicating that FLZ is worth further studies for fighting antisenescence and dementia.
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PMID:A novel cyclic squamosamide analogue compound FLZ improves memory impairment in artificial senescence mice induced by chronic injection of D-galactose and NaNO2. 1797 Oct 66

Previous studies have suggested that quetiapine, an atypical antipsychotic drug, may have beneficial effects on cognitive impairment, and be a neuroprotectant in treating neurodegenerative diseases. In the present study, we investigated the effects of quetiapine on memory impairment and pathological changes in an amyloid precursor protein (APP)/presenilin-1 (PS-1) double transgenic mouse model of Alzheimer's disease (AD). Non-transgenic and transgenic mice were treated with quetiapine (0, 2.5, or 5mg/(kg day)) for 1, 4, and 7 months in drinking water from the age of 2 months. After 4 and 7 months of continuous quetiapine administration, memory impairment was prevented, and the number of beta-amyloid (Abeta) plaques decreased in the cortex and hippocampus of the transgenic mice. Quetiapine also decreased brain Abeta peptides, beta-secretase activity and expression, and the level of C99 (an APP C-terminal fragment following cleavage by beta-secretase) in the transgenic mice. Furthermore, quetiapine attenuated anxiety-like behavior, up-regulated cerebral Bcl-2 protein, and decreased cerebral nitrotyrosine in the transgenic mice. These findings suggest that quetiapine can alleviate cognitive impairment and pathological changes in an APP/PS1 double transgenic mouse model of AD, and further indicate that quetiapine may have preventive effects in the treatment of AD.
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PMID:Beneficial effects of quetiapine in a transgenic mouse model of Alzheimer's disease. 1807 26

Several studies open up the possibility that chronic exposure to opioid drugs in the CNS would interfere with learning and memory through a neurotoxic effect related to activation of apoptotic pathways. Here, we have analyzed the effects of prolonged heroin administration on sensorimotor and cognitive performance in mice, as well as the associated changes in brain expression of proteins regulating the extrinsic (FasL and Fas) and the mitochondrial (Bcl-2, Bcl-X(L), Bad and Bax) apoptotic pathways. Our findings indicate that chronic heroin did not interfere with mice performance in a battery of sensorimotor tests. On the other hand, cognitive ability in the Morris water maze and cognitive flexibility-related performance were strongly impaired by chronic heroin. These effects were associated with up-regulation of pro-apoptotic proteins such as Fas, FasL and Bad, in the cortex and hippocampus, indicating the activation of both the death receptor and the mitochondrial apoptotic pathways. Another indicator of apoptosis was the presence of TUNEL (TdT-mediated dUTP nick-end labeling) positive cells scattered throughout the brain.
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PMID:Chronic administration of heroin to mice produces up-regulation of brain apoptosis-related proteins and impairs spatial learning and memory. 1820 31

7-[(3-piperidyl)-1-propinyl]-camptothecin (CPT21) is a novel semi-synthetic water-soluble analogue of camptothecin. In this context, we assessed the anti-tumor activity of CPT21 both in vivo and in vitro and explored its molecular mechanism. We found that CPT21 presented a broad anti-tumor spectrum against ten cancer cell lines in vitro, and the IC(50) values ranged from 0.1 to 12.0 microM. CPT21 was also capable to interrupt the DNA topoisemerase I activity and caused DNA double strand breaks during DNA replication. Proportion of apoptotic SGC7901 cells induced by CPT21 showed a time- and concentration-dependent increase accompanied with the decrease in mitochondria membrane potential (DeltaPsim). We also observed that CPT21 up-regulated the protein expression of p53, phospho-p53, p21, BAX, phospho-c-Jun NH2-terminal protein kinase (JNK), meanwhile down-regulating the protein expression of Bcl-2, procaspase-9, XIAP, and phospho-ERK1/2. In the study of SGC7901 xenograft model, the results suggested that both 5.0 mg/kg and 10.0 mg/kg CPT21 achieved high anti-tumor activity, and the tumor inhibition rates were 42.5% and 75.1% respectively. Taken together, our study demonstrates that CPT21 displays an extensive anti-tumor spectrum and CPT21 can induce the apoptosis of SGC7901 cells via activating the caspases cascade followed by disrupting mitochondrion function.
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PMID:CPT21, a novel compound with anti-proliferative effect against gastric cancer cell SGC7901. 1828 17


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