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)

Relatively few studies have been published with regard to modification of apoptosis in normal tissues as a function of ageing. The majority of these studies demonstrated an increase in programmed cell death (PCD) with age. However, opposite results, namely loss of apoptotic control with age, have also been reported. In the present study, we examined proliferation and apoptotic cell death in spleens of C57/BL mice of different ages. A tendency towards decrease in cell proliferative capacity was seen with age. By contrast, apoptosis was increased in spleens from aged animals. Moreover, the proliferative cell/apoptotic cell ratio decreased in function of age. Ladder type DNA degradation was much more pronounced in DNA derived from splenocytes of old mice. These results were supported by a decrease of Bcl-2 and an increase in Fas receptor expression as well as by increased activation of caspases 8, 3 and 9 in splenocytes from aged animals. In addition, cell surface molecular markers recognizable by macrophages in apoptotic cells, namely decreased sialic acid concomitant with increased unmasking of galactose residues, were more pronounced on splenocytes from old mice than on those from young animals. In addition to the experimental evidence which supports a role of apoptotic cell death in ageing, a series of theoretical reasoning, which could also favor this possibility, are discussed.
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PMID:Ageing-apoptosis relation in murine spleen. 1465 89

Because adverse effects of glucose were attributed to its increased routing through the hexosamine pathway (HBP), we inquired whether HBP activation affects pancreatic beta-cell survival. Exposure of human islets to high glucose resulted in increased apoptosis of beta-cells upon serum deprivation that was reversed by azaserine. Also, glucosamine, a direct precursor of the downstream product of the HBP, increased human beta-cells apoptosis upon serum deprivation, which was reversed by benzyl-2-acetamido-2-deoxy-alpha-d-galactopyranoside (BADGP), an inhibitor of protein O-glycosylation. These results were reproduced in RIN rat beta-cells. Glucosamine treatment resulted in inhibition of tyrosine-phosphorylation of the insulin receptor (IR), IRS-1, and IRS-2, which was associated with increased O-glycosylation. These changes caused impaired activation of the PI 3-kinase/Akt survival signaling that resulted in reduced GSK-3 and FOXO1a inactivation. BADGP reversed the glucosamine-induced reduction in insulin-stimulated phosphorylation of IR, IRS-1, IRS-2, Akt, GSK-3, and FOXO1a. Impaired FOXO1a inactivation sustained expression of the pro-apoptotic protein Bim, without affecting Bad, Bcl-XL, or Bcl-2 expression. These results indicate that hyperglycemia may increase susceptibility to apoptosis of human and rat beta-cell through activation of the HBP. Increased routing of glucose through this metabolic pathway results in impaired activation of the IR/IRSs/PI3-kinase/Akt survival pathway by induction of O-glycosylation of signaling molecules.
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PMID:Increased O-glycosylation of insulin signaling proteins results in their impaired activation and enhanced susceptibility to apoptosis in pancreatic beta-cells. 1505 79

Several lines of evidence support that beta-amyloid (Abeta)-induced neurotoxicity is mediated through the generation of reactive oxygen species (ROS) and elevation of intracellular calcium. In this study, we have investigated protective effects of sesaminol glucosides on Abeta-induced oxidative cell death in cultured rat pheochromocytoma (PC12) cells. Sesaminol glucoside (50-250microg/ml) decreased Abeta(25-35)-induced ROS generation, formation of 8-oxodG, a form of oxidative DNA and elevation of intracellular calcium level concomitant with prevention of apoptotic cell death dose dependently. Sesaminol glucoside (50-250microg/ml) also effectively decreased Abeta1-42 and ADDL form of Abeta1-42 as well as the combination of H2O2 with FeSO4-induced cell damages. In mechanistic study, sesaminol glucosides attenuated Abeta25-35-induced activation of redox transcription factor nuclear factor-kappaB NF-kappaB through inhibition of p50 translocation and IkappaB phosphorylation, and blocked NF-kappaB-dependent luciferase activity in addition to the inhibitory effect on Abeta25-35-induced activation of ERK kinase signal pathway. Consistent with the inhibitory effect on Abeta25-35-induced stress-induced cell death, sesaminol glucosides decreased expression of pro-apoptotic gene p53, and Bax and caspase-3, but enhanced expression of anti-apoptotic Bcl-2. Moreover, the protective effects of sesaminol glucoside on Abeta25-35-induced ROS generation, NF-kappaB activation and cell death were further enhanced with glutathione. This study therefore suggests that sesaminol glucosides have protective effect on Abeta-induced neuronal cell death, and its effect may be through antioxidative property.
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PMID:Effect of sesaminol glucosides on beta-amyloid-induced PC12 cell death through antioxidant mechanisms. 1588 33

4-Demethyl-picropodophyllotoxin 7'-O-beta-D-glucopyranoside (4DPG), a new podophyllotoxin glucoside, was isolated from the rhizomes of Sinopodophyllum emodi (Wall.) Ying and showed cytotoxic effects in human carcinoma cells. Among the target cells (HeLa, A2 and SH-SY5Y), the cytotoxic effects of 4DPG showed dose- and time-dependency. Furthermore, the cervical carcinoma cell line, HeLa, was more sensitive to 4DPG. Flow cytometric analysis demonstrated the presence of apoptotic cells with low DNA content, a decrease of cell population at the G1 phase, and a concomitant increase of cell population at the G2/M phase. 4DPG also caused DNA fragmentation in HeLa cells. Treatment with 0.1 microM 4DPG increased p53 expression and Bax/Bcl-2 ratio in HeLa cells, as well as in A2 cells. These results suggested that 4DPG-induced apoptosis might be through a p53-dependent pathway.
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PMID:Apoptosis induced by one new podophyllotoxin glucoside in human carcinoma cells. 1592 73

Anthocyanins are naturally occurring reddish pigments that abundant in fruits and vegetables. To investigate the mechanistic basis for the anti-tumor properties of anthocyanins, five aglycone (cyanidin, delphinidin, malvidin, pelargonidin, and peonidin) and four glycosylated (cyanidin-3-glucoside, malvidin-3-glucoside, pelargonidin-3-glucoside and peonidin-3-glucoside) anthocyanins were used to examine their effects on cell cycle progression and induction of apoptosis in human gastric adenocarcinoma AGS cells. The data from cell viability assay showed that malvidin exhibited the most potent anti-proliferation effect on AGS cells in a time- and dose-dependent manner (P<0.05). This event is accompanied the arrest of AGS cells at the G0/G1 phase by malvidin at the tested concentrations of 0-200 microM. Cellular uptake of anthocyanin and anthocyanidin was confirmed by HPLC analysis and the intracellular accumulation of malvidin (24.9+/-1.1 microM/mg protein) was observed when treatment of AGS cells with malvidin for 12 h. In addition, an accumulation of AGS cells in sub-G1 phase (20% and 30% increase for 100 and 200 microM of malvidin, respectively) was observed as well as by the appearance of a fraction of cells with an aneudiploid DNA content. The occurrence of apoptosis induced by malvidin was confirmed by morphological and biochemical features, including apoptotic bodies formation, caspase-3 activation and poly(ADP-ribose) polymerase proteolysis. Furthermore, the mitochondrial membrane potential of apoptotic cells after treatment with malvidin was significantly lost and resulted in the elevation of Bax/Bcl-2 ratio for 1.6-fold against control for 100 microM treatment. In addition, the malvidin treatment significantly increased the p38 kinase expression and inhibited the ERK activity, and the effects of malvidin on caspase-3 activation were blocked, respectively, by the ERK and p38 inhibitors. These findings suggest that growth inhibition and cytotoxicity of AGS cells by malvidin is involved in the induction of apoptosis rather than necrosis.
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PMID:Effects of anthocyanidin on the inhibition of proliferation and induction of apoptosis in human gastric adenocarcinoma cells. 1596 18

Apoptosis of arterial cells induced by oxidized low-density lipoprotein (oxLDL) is thought to contribute to the progression of vascular dysfunction and atherogenesis. It is well established that diabetes mellitus is accompanied by both glycosylation and oxidation LDL, but the biological effects of these modified lipoproteins are poorly understood. We demonstrate here that glycosylated oxLDL (glc-oxLDL) promotes apoptotic signaling in human coronary smooth muscle cells. This was associated by a decrease of the antiapoptotic protein Bcl-2, an increase of the pro-apoptotic protein Bax, and activation of caspase 3. Glc-oxLDL also activated NFK: B and decreased IK: B, these effects were more pronounced than those achieved with oxLDL. Our study shows that glc-oxLDL influences a broad cascade of signaling transduction pathways, which may not only result in apoptosis, but also could affect NFkappaB in human coronary cells. This cascade of events may influence the evolution of atherogenesis and vascular complications in diabetic patients.
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PMID:Glycoxidation of low-density lipoprotein promotes multiple apoptotic pathways and NFkappaB activation in human coronary cells. 1626 96

Previous studies have shown that injection of D-galactose could result in senescent performances in animals, that injection of NaNO2 could cause ischaemia and hypoxia in many organs, and combined injection of D-galactose and NaNO2 make normal mice taking on senescent performances in a shorter period. The aim of this study was to investigate the effects of CE, an extract from a Tibetan medicinal herb, Coeloglossum. viride (L.) Hartm. var. bracteatum (Willd.), on senescent mice. The step-down test was performed to evaluate the learning and memory function of mice. The activities of superoxide dismutase, adenosine triphosphatase, monoamine oxydase and the content of malondialdehyde were measured to determine the impairment of brain. The expressions of Bcl-2, Bax, and caspase-3 proteins in mouse hippocampus were studied by immunohistochemical staining. The data demonstrated that D-galactose and NaNO2 treated mice had significant deficits in learning and memory function. The reduced activities of superoxide dismutase, adenosine triphosphatase, increased activities of monoamine oxydase and level of malondialdehyde were also found. Bax and caspase-3 positive cells increased while Bcl-2 positive cells decreased remarkably. Treatment of CE (2.5, 5 mg.kg(-1)) ameliorated the memory impairment; rectified the biochemistry and neural system changes in mice. These results suggest that CE offers promise as a tool for treatment of senescence-related diseases.
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PMID:Effects of Coeloglossum. viride var. bracteatum extract on memory deficits and pathological changes in senescent mice. 1643 92

Mesangial cell apoptosis occurs in experimental diabetic nephropathy, and this correlates with worsening albuminuria. This study examines the mechanism by which glucose modulates mesangial cell apoptosis. Apoptosis was induced in mesangial cells by serum deprivation in the presence of 5 or 25 mM D-glucose, and examined by expression of Annexin-V and disruption of mitochondrial transmembrane potential. Involvement of Bax, Bcl-2 and NF-kappaB were examined by RT-PCR and EMSA. Involvement of TGF-beta1 was sought by determining the effect of recombinant TGF-beta1on apoptosis and the mediators of the apoptotic pathway (Bcl2/Bax and NF-kappaB). Culture of cells in the presence of 25 mM D-glucose (i) enhanced apoptosis stimulated by serum depletion, (ii) enhanced activation of caspase-3, (iii) inhibited NF-kappaB activation, and (iv) decreased Bcl-2:Bax ratio. Inhibition of NF-kappaB using SN50, also increased mesangial cell apoptosis, and decreased Bcl-2:Bax ratio. Addition of TGF-beta1 to mesangial cells mimicked the effect of high glucose reducing NF-kappaB expression and Bcl-2:Bax ratio. Furthermore glucose-mediated enhanced apoptosis was inhibited by the addition of a blocking antibody to TGF-beta1. Exposure of mesangial cells to 25 mM D-glucose stimulated the generation of both total and active TGF-beta1 in the cell culture supernatant, this increase was only significant after 48-72 h, that is at a time point later than enhanced apoptosis. Addition of 25 mM D-glucose, however, increased sensitivity of mesangial cells to TGF-beta1 as assessed by luciferase activity of a Smad sensitive reporter construct. The data suggest that elevated glucose concentration enhanced the pathway leading to apoptosis following serum deprivation. Furthermore, it is likely that this is dependent on glucose-mediated enhanced sensitivity to endogenous TGF-beta1 rather than glucose stimulated de novo TGF-beta1 synthesis.
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PMID:Glucose enhances mesangial cell apoptosis. 1658 41

Thiazolidinediones are ligands for peroxisome proliferator-activated receptor (PPAR)-gamma, widely used as insulin sensitizer in type 2 diabetic patients and implicated in apoptosis, cell proliferation, and cell cycle regulation. Here, the effect of thiazolidinediones on G1-phase cell cycle arrest, the hallmark in diabetic nephropathy, was investigated. Eight-week-old male Otsuka Long-Evans Tokushima fatty rats were treated with pioglitazone (1 mg x kg body wt(-1) x day(-1)) until 50 weeks of age and compared with insulin treatment. Although similar HbA(1c) levels were observed in both groups, pioglitazone significantly inhibited glomerular hypertrophy and mesangial matrix expansion and reduced urinary albumin excretion compared with the insulin-treated group. In addition, pioglitazone significantly reduced the number of glomerular p27(Kip1)-positive cells. Because prominent expression of PPAR-gamma was observed in podocytes in glomeruli and cultured cells, conditionally immortalized mouse podocyte cells were cultured under 5.5 and 25 mmol/l D-glucose supplemented with pioglitazone. Pioglitazone inhibited cell hypertrophy revealed by [(3)H]thymidine and [(3)H]proline incorporation, and pioglitazone reversed high glucose-induced G1-phase cell cycle arrest, i.e., an increase in G0/G1 phase and decrease in S and G2 phases. Pioglitazone suppressed high glucose-induced phosphorylation of p44/42 mitogen-activated protein kinase and reduced Bcl-2 and p27(Kip1) protein levels. Besides glucose-lowering action, pioglitazone ameliorates diabetic nephropathy via cell cycle-dependent mechanisms.
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PMID:Thiazolidinediones ameliorate diabetic nephropathy via cell cycle-dependent mechanisms. 1673 29

The purpose of this study was to explore the neuroprotective effects of daidzein on the apoptotic pathway in the hippocampus and cortex of D-galactose treated mice. For this purpose we have examined the expression of bcl-2 mRNA, bax mRNA and caspase-3 in the hippocampus and cortex of D-galactose-treated mice after fed with 10 or 5 mg/kg of daidzein. The results of in situ hybridization experiments indicate that daidzein could help increase the transcriptions of bcl-2 and decrease the transcriptions of bax in those brain regions of D-galactose-treated mice. Furthermore, immunohistochemical studies showed that daidzein could reduce the expression of caspase-3 in both brain regions. These results suggest that daidzein in soybean can inhibit the D-gal induced apoptosis via Bcl-2/Bax apoptotic pathway and be a potential medical candidate for neurodegeneration therapy.
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PMID:The anti-apoptosis effects of daidzein in the brain of D-galactose treated mice. 1790 1


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