UNIPROT:P10415 - FACTA Search

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Query: UNIPROT:P10415 (Bcl-2)
33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Previously we demonstrated that insulin protects against neuronal oxidative stress by restoring antioxidants and energy metabolism. In this study, we analysed how insulin influences insulin-(IR) and insulin growth factor-1 receptor (IGF-1R) intracellular signaling pathways after oxidative stress caused by ascorbate/Fe2+ in rat cortical neurons. Insulin prevented oxidative stress-induced decrease in tyrosine phosphorylation of IR and IGF-1R and Akt inactivation. Insulin also decreased the active form of glycogen synthase kinase-3beta (GSK-3beta) upon oxidation. Since phosphatidylinositol 3-kinase (PI-3K)/Akt-mediated inhibition of GSK-3beta may stimulate protein synthesis and decrease apoptosis, we analysed mRNA and protein expression of "candidate" proteins involved in antioxidant defense, glucose metabolism and apoptosis. Insulin prevented oxidative stress-induced increase in glutathione peroxidase-1 and decrease in hexokinase-II expression, supporting previous findings of changes in glutathione redox cycle and glycolysis. Moreover, insulin precluded Bcl-2 decrease and caspase-3 increased expression. Concordantly, insulin abolished caspase-3 activity and DNA fragmentation caused by oxidative stress. Thus, insulin-mediated activation of IR/IGF-1R stimulates PI-3K/Akt and inhibits GSK-3beta signaling pathways, modifying neuronal antioxidant defense-, glucose metabolism- and anti-apoptotic-associated protein synthesis. These and previous data implicate insulin as a promising neuroprotective agent against oxidative stress associated with neurodegenerative diseases.
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PMID:Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signaling pathways and changes in protein expression. 1834 71

Maternal diabetes affects the development of the offspring by altering the uterine environment. We aimed to investigate the extent to which the blood flow (measured as Tissue Perfusion Units; TPU) to implantation sites and the expression of developmentally important genes in the offspring are affected by maternal diabetes. We measured mRNA levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), Bcl-2 associated X protein (Bax), B-cell lymphoma protein (Bcl-2), tumor suppressor protein-53 (p53), paired box protein-3 (Pax-3) and vascular endothelial growth factor-A (Vegf-A). Moreover, we studied the effect on uterine blood flow (TPU) and the expression of the genes exerted by embryonic maldevelopment (malformation or resorption). Streptozotocin induced diabetic (D) and non-diabetic (N) pregnant rats were used in the study. Blood flow (TPU) to implantation sites was measured by a laser Doppler flow meter, and gene expression was analyzed by RT-PCR. Maternal diabetes caused increased blood flow (TPU) to implantation sites compared with normal pregnancy. Furthermore, implantation sites of D rats containing malformed offspring showed impaired growth and decreased blood flow (TPU) compared with their littermates at all gestational days. Resorbed offspring from both N and D rats displayed increased blood flow (TPU) compared with their non-resorbed littermates. Moreover, we found that maternal diabetes causes decreased expression of genes involved in the oxidative stress defense system (CuZnSOD in non-malformed D11 embryos, MnSOD at all gestational time points, ECSOD and Gpx-1 at GD11-GD15, CAT and Gpx-2 at GD15), decreased expression of Pax-3 at GD11, and increased expression of Vegf-A at all gestational time points. We conclude that both maternal metabolism and embryonic developmental state affect the blood flow (TPU) to the implantation site. Maternal diabetes causes decreased expression of anti-oxidative enzymes and enhanced angiogenesis in the offspring in rats.
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PMID:Altered uterine perfusion is involved in fetal outcome of diabetic rats. 1838 70

The multifunctional, anti-Alzheimer drug, ladostigil (TV3326) [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate] combines the neuroprotective effects of the anti-Parkinson drug, rasagiline, a selective monoamine oxidase (MAO)-B inhibitor, with the cholinesterase (ChE) inhibitory activity of rivastigmine in a single molecule. Ladostigil has been shown to possess potent antiapoptotic and neuroprotective activities in various oxidative insults in vitro and in vivo, such as prevention of the fall in mitochondrial membrane potential and regulation of Bcl-2 family proteins. In the present study, we demonstrate that ladostigil (1 microM) increased cell viability, associated with the increase of catalase activity and decrease of intracellular reactive oxygen species (ROS) production in human SH-SY5Y neuroblastoma cells exposed to (hydrogen peroxide) H(2)O(2). Furthermore, ladostigil significantly elevated mRNA levels of the antioxidants enzymes, catalase, NAD(P)H quinone oxidoreductase 1 (NQO1) and peroxiredoxin 1 (Prx 1) in H(2)O(2)-treated SH-SY5Y cells. Chronic treatment with ladostigil (1 mg/kg gavage per day for 30 days) markedly up-regulated mRNA expression levels of various antioxidant enzymes in aged rat hippocampus (e.g. glutathione peroxidase precursor (GSHPX-P), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PD)). These findings indicate that in addition to its multiple neuroprotective characteristics, ladostigil also possesses antioxidant properties, which might be beneficial for the treatment of oxidative stress (OS) in aging and age-associated neurodegenerative diseases.
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PMID:The neuroprotective effect of ladostigil against hydrogen peroxide-mediated cytotoxicity. 1859 87

Aminoacetone (AA), triose phosphates, and acetone are putative endogenous sources of potentially cytotoxic and genotoxic methylglyoxal (MG), which has been reported to be augmented in the plasma of diabetic patients. In these patients, accumulation of MG derived from aminoacetone, a threonine and glycine catabolite, is inferred from the observed concomitant endothelial overexpression of circulating semicarbazide-sensitive amine oxidases. These copper-dependent enzymes catalyze the oxidation of primary amines, such as AA and methylamine, by molecular oxygen, to the corresponding aldehydes, NH4(+) ion and H2O2. We recently reported that AA aerobic oxidation to MG also takes place immediately upon addition of catalytic amounts of copper and iron ions. Taking into account that (i) MG and H2O2 are reportedly cytotoxic to insulin-producing cell lineages such as RINm5f and that (ii) the metal-catalyzed oxidation of AA is propagated by O2(*-) radical anion, we decided to investigate the possible pro-oxidant action of AA on these cells taken here as a reliable model system for pancreatic beta-cells. Indeed, we show that AA (0.10-5.0 mM) administration to RINm5f cultures induces cell death. Ferrous (50-300 microM) and Fe(3+) ion (100 microM) addition to the cell cultures had no effect, whereas Cu(2+) (5.0-100 microM) significantly increased cell death. Supplementation of the AA- and Cu(2+)-containing culture medium with antioxidants, such as catalase (5.0 microM), superoxide dismutase (SOD, 50 U/mL), and N-acetylcysteine (NAC, 5.0 mM) led to partial protection. mRNA expression of MnSOD, CuZnSOD, glutathione peroxidase, and glutathione reductase, but not of catalase, is higher in cells treated with AA (0.50-1.0 mM) plus Cu(2+) ions (10-50 microM) relative to control cultures. This may imply higher activity of antioxidant enzymes in RINm5f AA-treated cells. In addition, we have found that AA (0.50-1.0 mM) plus Cu(2+) (100 microM) (i) increase RINm5f cytosolic calcium; (ii) promote DNA fragmentation; and (iii) increase the pro-apoptotic (Bax)/antiapoptotic (Bcl-2) ratio at the level of mRNA expression. In conclusion, although both normal and pathological concentrations of AA are probably much lower than those used here, it is tempting to propose that excess AA in diabetic patients may drive oxidative damage and eventually the death of pancreatic beta-cells.
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PMID:Aminoacetone, a putative endogenous source of methylglyoxal, causes oxidative stress and death to insulin-producing RINm5f cells. 1872 31

Epigallocatechin-3-gallate (EGCG) is a major flavonoid component of green tea that displays antiapoptotic effects in numerous models of neurotoxicity. Although the intrinsic free radical scavenging activity of EGCG likely contributes to its antiapoptotic effect, other modes of action have also been suggested. We systematically analyzed the antiapoptotic action of EGCG in primary cultures of rat cerebellar granule neurons (CGNs). The dose-dependent protective effects of EGCG were determined after coincubation with eight different stimuli that each induced neuronal apoptosis by distinct mechanisms. Under these conditions, EGCG provided significant neuroprotection only from insults that induce apoptosis by causing mitochondrial oxidative stress. Despite this selective antiapoptotic effect, EGCG did not significantly alter the endogenous activities or expression of Mn(2+)- superoxide dismutase, glutathione peroxidase, Nrf2, or Bcl-2. Subfractionation of CGNs after incubation with (3)H-EGCG revealed that a striking 90-95% of the polyphenol accumulated in the mitochondrial fraction. These data demonstrate that EGCG selectively protects neurons from apoptosis induced by mitochondrial oxidative stress. This effect is likely due to accumulation of EGCG in the mitochondria, where it acts locally as a free radical scavenger. These properties of EGCG make it an interesting therapeutic candidate for neurodegenerative diseases involving neuronal apoptosis triggered by mitochondrial oxidative stress.
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PMID:Green tea epigallocatechin 3-gallate accumulates in mitochondria and displays a selective antiapoptotic effect against inducers of mitochondrial oxidative stress in neurons. 1875 8

The effects of acute perfluorododecanoic acid (PFDoA) exposure on the induction of oxidative stress and alteration of mitochondrial gene expression were studied in the livers of female zebrafish (Danio rerio). Female zebrafish were exposed to PFDoA via a single intraperitoneal injection (0, 20, 40, or 80 microg PFDoA/g body weight) and were then sacrificed 48 h, 96 h, or seven days post-PFDoA administration. PFDoA-treated fish exhibited histopathological liver damage, including swollen hepatocytes, vacuolar degeneration, and nuclei pycnosis. Glutathione (GSH) content and catalase (CAT) activity decreased significantly at 48 h post-injection while superoxide dismutase (SOD) activity was initially decreased at 48 h post-injection but was then elevated by seven days post-injection. The activity of glutathione peroxidase (GPx) increased at 48 h and seven days compared to control fish, although the increased level at seven days post-injection was decreased compared to the level at 48 h post-injection. Lipid peroxidation levels were increased at seven days post-injection, while no apparent induction was observed at 48 h or 96 h post-injection. The mRNA expression of medium-chain fatty acid dehydrogenase (MCAD) was induced, while the transcriptional expression of liver fatty acid binding protein (L-FABP), peroxisome proliferating activating receptor alpha (PPARalpha), carnitine palmitoyl-transferase I (CPT-I), uncoupling protein 2 (UCP-2), and Bcl-2 were significantly inhibited. Furthermore, the transcriptional expression of peroxisomal fatty acyl-CoA oxidase (ACOX), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD) did not exhibit significant changes following PFDoA treatment. No significant changes were noted in the transcriptional expression of genes involved in mitochondrial respiratory chain and ATP synthesis, including cytochrome c oxidase subunit I (COXI), NADH dehydrogenase subunit I (NDI), and ATP synthase F0 subunit 6 (ATPo6). These results demonstrate that turbulence of fatty acid beta-oxidation and oxidative stress responses were involved in the PFDoA-induced hepatotoxicity.
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PMID:Induction of time-dependent oxidative stress and related transcriptional effects of perfluorododecanoic acid in zebrafish liver. 1876 Aug 46

Peroxiredoxin II, a cytosolic isoform of the antioxidant enzyme family, has been implicated in cancer-associated cell death and apoptosis, but its functional role in the heart remains to be elucidated. Interestingly, the expression levels of peroxiredoxin II were decreased in mouse hearts upon ischemia-reperfusion, while they were elevated in two genetically modified hyperdynamic hearts with phospholamban ablation or protein phosphatase 1 inhibitor 1 overexpression. To delineate the functional significance of altered peroxiredoxin II expression, adenoviruses encoding sense or antisense peroxiredoxin II were generated; cardiomyocytes were infected, and then subjected to H(2)O(2) treatment to mimic oxidative stress-induced cell death and apoptosis. H(2)O(2) stimulation resulted in a significant decrease of endogenous peroxiredoxin II expression, along with reduced cell viability in control cells. However, overexpression of peroxiredoxin II significantly protected from H(2)O(2)-induced apoptosis and necrosis, while downregulation of this enzyme promoted the detrimental effects of oxidative stress in cardiomyocytes. The beneficial effects of peroxiredoxin II were associated with increased Bcl-2 expression, decreased expression of Bax and attenuated activity of caspases 3, 9 and 12. Furthermore, there were no significant alterations in the expression levels of the other five isoforms of peroxiredoxin, as well as active catalase or glutathione peroxidase-1 after ischemia-reperfusion or H(2)O(2) treatment. These findings suggest that peroxiredoxin II may be a unique antioxidant in the cardiac system and may represent a potential target for cardiac protection from oxidative stress-induced injury.
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PMID:Protection of peroxiredoxin II on oxidative stress-induced cardiomyocyte death and apoptosis. 1903 Sep 11

The aims of this study were to assess the effects of a swimming session on the peripheral blood neutrophil and lymphocyte pro- and antioxidant system, identify any differences between the sexes and the regulatory mechanisms that might induce the immune cell adaptive response to exercise. Twenty-four swimmers (15 males, 9 females) participated in a one-hour swimming session at 75-80% of their maximal capacity. The session induced neutrophilia and decreased antioxidant enzyme activities and ascorbate levels in neutrophils. Malondialdehyde rose in neutrophils in males and females, whereas the carbonyl index only increased in males. Lymphocyte glutathione peroxidase activity was higher in males at baseline and rose as a consequence of exercise. The exercise decreased uncoupling protein-3 and Bcl-2 gene expression. The expression of PPARgamma coactivator-1 alpha (PGC-1alpha) correlated positively with that of sirtuin 3 (SIRT3) and catalase. In summary, a swimming session of one hour at 75-80% of maximal capacity produced oxidative damage in neutrophils and induced the antioxidant defences in lymphocytes. PGC-1alpha and SIRT3 appear to be key effectors of this adaptive response in lymphocytes. Both the neutrophil and lymphocyte response to exercise were slightly weaker in females than males.
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PMID:Antioxidant regulatory mechanisms in neutrophils and lymphocytes after intense exercise. 1903 35

Glycyrrhizic acid (GA) and 18beta-glycyrrhetinic acid (18betaGA) are the bioactive compounds of licorice. The neuroprotective effects of GA and 18betaGA against serum/glucose deprivation and 6-hydroxydopamine (6-OHDA)-induced cytotoxicity in PC12 cells were investigated. The intracellular reactive oxygen species (ROS) content, the activity of the antioxidant enzymes of glutathione peroxidase (GPx) and catalase, the mitochondrial membrane potential (MMP), and the mitochondrial Bax/Bcl-2 ratio were determined. PI3K/Akt pathway signaling was also evaluated to study the possible protective mechanism. The results showed that GA treatment decreased the ROS content by elevating the activities of GPx and catalase, leading to a decreased MMP. GA and 18betaGA also lowered the mitochondrial Bax/Bcl-2 ratio and activated PI3K/Akt signal. The results suggest that GA may protect PC12 cells from ischemic injury via modulation of the intracellular antioxidant system and mitochondria-induced apoptosis. Moreover, GA and 18betaGA may modulate the ratio of the mitochondrial Bcl-2 family and influence PI3K/Akt signaling. These results demonstrate the neuroprotective ability of GA and 18betaGA and suggest that the cytotoxicity of 6-OHDA may influence the mitochondrial Bax/Bcl-2 ratio without altering the expression of Bax. This study also suggests a possible compound for treating neural disease and general neuronal health.
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PMID:Neuroprotective effects of glycyrrhizic acid and 18beta-glycyrrhetinic acid in PC12 cells via modulation of the PI3K/Akt pathway. 1910 45

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