UNIPROT:P04637 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloid beta-peptide (Abeta) contributes to the pathogenesis of Alzheimer's disease (AD), causing neuronal death through apoptosis. In this study, the neuroprotective role of small peptides, Gly-Pro-Glu (GPE), Gly-Glu (GE), Gly-Pro-Asp (GPD), and Gly-Pro-Arg (GPR) were examined against Abeta-induced toxicity in cultured rat hippocampal neurons. We report here that GPR (10-100 microM) prevented Abeta-mediated increase in lactate dehydrogenase (LDH) release and Abeta inhibition of MTT reduction, even in neurons that were pre-exposed to Abeta for 24 or 48 h. Since GPR prevented Abeta inhibition of MTT reduction, the anti-apoptotic effect of GPR was studied by examining activation of caspase-3 and expression of p53 protein. Caspase-3 was significantly activated by 20 microM Abeta25-35 and 5 microM Abeta1-40, but GPR effectively prevented the Abeta-mediated activation of caspase-3. Similarly, Abeta increased numbers of p53-positive cells, but GPR prevented this Abeta effect. Our findings suggest that GPR can rescue cultured rat hippocampal neurons from Abeta-induced neuronal death by inhibiting caspase-3/p53-dependent apoptosis.
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PMID:A three amino acid peptide, Gly-Pro-Arg, protects and rescues cell death induced by amyloid beta-peptide. 1476 84

We have investigated the dose (in the range of microM) and time-dependent effects of four different retinoids (retinol, retinal, retinoic acid and retinol palmitate) on human dermal fibroblasts cultivated in vitro. Retinol and retinal, at a concentration of 20 microM, caused cell damage as evaluated by lactate dehydrogenase activity released into the culture medium. The oxidised glutathione (GSSG)/reduced glutathione (GSH) ratio and malondialdehyde production indicated that 20 microM of retinol provoked oxidative stress in the cultivated human fibroblasts. In the first 8 h after retinol treatment the levels of p53 and Bax proteins as well as caspase 3 activity increased, suggesting apoptotic cell death during the first hours of treatment. If the retinol treatment exceeded 18-24 h we observed necrotic cell death. Vitamin E and coenzyme Q(10) had a protective effect against oxidative stress generated by retinol. Both antioxidant molecules reduced retinol uptake, and in the case of vitamin E the expression of CRABP-II mRNA was induced, providing a plausible explanation for its protective effect.
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PMID:Retinol, at concentrations greater than the physiological limit, induces oxidative stress and apoptosis in human dermal fibroblasts. 1500 15

Rituximab is widely used for the treatment of B-cell non-Hodgkin's lymphoma (NHL), and encouraging results have been obtained. However, some CD20-positive NHL show minimal response to rituximab, indicating that the treatment effect depends on the presence or absence of an unidentified factor. We analyzed the relationship between the effect of rituximab plus chemotherapy and expression of Ki-67, p53 and bcl-2 and several clinical variables in cases of B-NHL, particularly follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Forty-four patients were included in the present study, and the overall treatment response rate was 68%. Twelve of 30 patients (40%) achieved a complete response, five (16%) reached an unconfirmed complete response and 13 (43%) achieved a partial response. A high serum lactate dehydrogenase level and International Prognostic Index of high or high intermediate risk were associated with a decreased response in the case of FL. Immunohistochemical assays were performed in 18 FL patients (55%) and 15 DLBCL patients (45%). Significant correlation was found between an inferior response to treatment and high Ki-67 expression in the cases of FL (P = 0.006). p53 and bcl-2 expression did not correlate significantly with the response rate. The cell cycle appears to be an important factor in the efficacy of rituximab treatment. Ki-67 expression might be a predictor of efficacy of rituximab plus chemotherapy.
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PMID:Efficacy of rituximab plus chemotherapy in follicular lymphoma depends on Ki-67 expression. 1536 34

Polybrominated diphenyl ethers (PBDEs) are an important class of flame retardants. Because of their presence in maternal milk and their structural similarity to polychlorinated biphenyls (PCBs), concern has been raised on their possible developmental neurotoxicity. Aim of the present study was to investigate the in vitro effects of PBDE-99 (2,2', 4,4', 5-pentabromodiphenyl ether) on astroglial cells (human 132-1N1 astrocytoma cells) and comparing it with those of the PCB mixture Aroclor 1254. Both PBDE-99 and Aroclor 1254 caused a concentration-dependent inhibition of MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction, however, only the latter increased lactate dehydrogenase (LDH) release or cell death, assessed by the trypan blue assay. PBDE-99 caused translocation of the three protein kinase C (PKC) isozymes (alpha, epsilon, zeta) present in 132-1N1 astrocytoma cells, while Aroclor 1254 affected only PKCalpha and epsilon translocation. However, pre-incubation with the PKC inhibitor GF109203X or PKC down-regulation by the phorbol ester PMA, had minimal or no effect on PBDE-99 or Aroclor 1254-induced cytotoxicity. Similarly, the calcium chelator BAPTA-AM, the tyrosine kinase inhibitor genistein, and the MEK (mitogen activated protein kinase kinase) inhibitor PD98059 had no effect on PBDE-99 and Aroclor 1254 cytoxicity. On the other hand, the phosphatidylinositol 3 kinase (PI-3K) inhibitor LY290042 enhanced PBDE-99 toxicity, but did not affect Aroclor 1254. Because of the involvement of PI-3K in apoptotic cell death, the ability of PBDE-99 and Aroclor 1254 to induce apoptosis in astrocytoma cells was investigated. PBDE-99, but not Aroclor 1254, caused apoptotic cell death in astrocytoma cells, assessed by the TUNEL method and by Hoechst 33258 staining, via a p53 dependent mechanism. These results suggest that PBDE-99 and Aroclor 1254 exert differential cytotoxic effects on human astroglial cells.
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PMID:Differential in vitro neurotoxicity of the flame retardant PBDE-99 and of the PCB Aroclor 1254 in human astrocytoma cells. 1547 74

Pyrrolidinedithiocarbamate (PDTC) is a potent antioxidant and an inhibitor of nuclear factor-kappaB (NF-kappaB). The present study examined the impact of PDTC preconditioning on gastric protection in response to ischemia-reperfusion (I/R) injury to the rat stomach. Male Wistar rats were recruited and divided into 3 groups (n = 7). One group was subjected to gastric ischemia for 30 min and reperfusion for 1 hour. The second group of rats was preconditioned with PDTC (200 mg/kg body mass i.v.) 15 min prior to ischemia and before reperfusion. The third group of rats was sham-operated and served as the control group. Gastric I/R injury increased serum lactate dehydrogenase level, vascular permeability of gastric mucosa (as indicated by Evans blue dye extravasation) and gastric content of inflammatory cytokine; tumor necrosis factor-alpha (TNF-alpha). Moreover, oxidative stress was increased as indicated by elevated lipid peroxides formation (measured as thiobarbituric acid reactive substances) and depleted reduced glutathione in gastric tissues. NF-kappaB translocation was also detected by electrophoretic mobility shift assay. Microscopically, gastric tissues subjected to I/R injury showed ulceration, hemorrhages, and neutrophil infiltration. Immunohistochemical studies of gastric sections revealed increased expression of p53 and Bcl-2 proteins. PDTC pretreatment reduced Evans blue extravasation, serum lactate dehydrogenase levels, gastric TNF-alpha levels, and thiobarbituric acid reactive substances content, and increased gastric glutathione content. Moreover, PDTC pretreatment abolished p53 expression and inhibited NF-kappaB translocation. Finally, histopathological changes were nearly restored by PDTC pretreatment. These results clearly demonstrate that NF-kappaB activation and pro-apoptotic protein p53 induction are involved in gastric I/R injury. PDTC protects against gastric I/R injury by an antioxidant, NF-kappaB inhibition, and by reduction of pro-apoptotic protein p53 expression, which seems to be downstream to NF-kappaB, thus promoting cell survival.
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PMID:Nuclear factor-kappaB inhibition by pyrrolidinedithiocarbamate attenuates gastric ischemia-reperfusion injury in rats. 1604 48

Using human neuroblastoma SH-SY5Y cells, effects of acrylamide on p53 protein and intracellular signal transducting pathways were examined. Acrylamide increased p53, phosphorylated p53, and p53-associated protein murine double minute 2 (MDM2). The phosphorylation of p53 was specific for the Ser15 site. Among mitogen-activated protein kinases (MAPKs), acrylamide caused phosphorylation of extracellular signal-regulated protein kinase (ERK) and p38 but not c-Jun NH(2)-terminal kinase. Nevertheless, blocking p38 pathway by LL-Z1640-2 did not suppress the phosphorylation of p53 at Ser15. In contrast, a specific inhibitor of ERK kinase (U0126 or PD98059) could abolish the accumulation as well as the phosphorylation of p53 at Ser15. Elevation of MDM2 was also abolished by U0126. An inhibitor of phosphatidylinositol 3-kinase-related kinase (PIKK) pathway (wortmannin) suppressed the increase of p53 and its phosphorylation at Ser15. Hence, acrylamide increases p53 protein and its phosphorylation at Ser15 through ERK and/or PIKK pathways. On the other hand, U0126 and PD98059 suppressed to some extent the cytotoxicity of acrylamide evaluated by trypan blue exclusion and lactate dehydrogenase (LDH) leakage, whereas neither LL-Z1640-2 nor wortmannin was effective in suppressing the toxicity. Thus, ERK pathway seems to play a role both in causing the phosphorylation of p53 at Ser15 and in the cytotoxicity of acrylamide in SH-SY5Y cells.
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PMID:Involvement of the extracellular signal-regulated protein kinase pathway in phosphorylation of p53 protein and exerting cytotoxicity in human neuroblastoma cells (SH-SY5Y) exposed to acrylamide. 1618 10

Tetrazolium violet (TV), a potent anticancer agent, has been shown to induce cell growth-inhibition in tumor cells. However, the related mechanism has not been revealed yet. In this report we assessed the influence of TV on cell growth and cell cycle in brain tumor cells. Treatment of C6 tumor cells with TV (5-15 microM for 24-72 h) resulted in a growth inhibition in a dose and time-dependent manner and G0/G1 phase arrest, determined by flow cytometry analysis. These effects were accompanied by apoptosis other than necrosis, evidenced by nuclear condensation, terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay and trypan blue exclusion assay plus lactate dehydrogenase (LDH) release assay. Treatment of cells with TV at 15 microM for 24 h resulted in an increase in the activity of caspase-3, evidenced by colorimetric assay, and a dramatic up-regulation of p53, accompanied with a significant increase of Bax/Bcl-2 ratio, as evidenced by immunofluorescence assay. These results suggest that TV induces growth inhibition of C6 cells through p53-midiated apoptotic pathway and G0/G1 checkpoint mechanism. Although detailed mechanisms remain to be explored, selective blockage of tumor cells in G0/G1 phase accompanied by p53-associated apoptosis makes tetrazolium violet a promising anticancer agent, meriting further investigations.
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PMID:Tetrazolium violet induces G0/G1 arrest and apoptosis in brain tumor cells. 1631 59

Spore-extracted toxins of the indoor mold Stachybotrys chartarum (SC) caused cytotoxicity (release of lactate dehydrogenase), inhibition of cell proliferation, and cell death in murine alveolar macrophage cell line MH-S in a dose- and time-dependent manner. Apoptotic cell death, confirmed based on morphological changes, DNA ladder formation, and caspase 3/7 activation, was detectable as early as at 3 h during treatment with a toxin concentration of 1 spore equivalent/macrophage and was preceded by DNA damage beginning at 15 min, as evidenced by DNA comet formation in single cell gel electrophoresis assay. The apoptotic dose of SC toxins did not induce detectable nitric oxide and pro-inflammatory cytokines (IL-1beta, IL-6, and TNF-alpha) but showed exacerbated cytotoxicity in presence of a non-apoptotic dose of the known pro-inflammatory agent LPS (10 ng/ml). Intracellular reduced glutathione (GSH) level showed a significant decrease beginning at 9 h of the toxin treatment whereas oxidized glutathione (GSSG) showed a corresponding significant increase, indicating a delayed onset of oxidative stress in the apoptosis process. The toxin-treated macrophages accumulated p53, an indicator of DNA damage response, and showed activation of the stress-inducible MAP kinases, JNK, and p38, in a time-dependent manner. Chemical blocking of either p38 or p53 inhibited in part the SC toxin-induced apoptosis whereas blocking of JNK did not show any such effect. This study constitutes the first report on induction of DNA damage and associated p53 activation by SC toxins, and demonstrates the involvement of p38- and p53-mediated signaling events in SC toxin-induced apoptosis of alveolar macrophages.
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PMID:DNA damage, redox changes, and associated stress-inducible signaling events underlying the apoptosis and cytotoxicity in murine alveolar macrophage cell line MH-S by methanol-extracted Stachybotrys chartarum toxins. 1647 59

Fas (CD95/APO-1) is a protein that is mainly related to apoptosis of lymphoid cells. The increment of Fas expression is associated with long-term survival in various malignancies. However, there are limited studies regarding the effect of Fas expression on the course and prognosis of non-Hodgkin's lymphoma. The aim of this study was to investigate the significance of immunohistochemical Fas expression on the prognosis of nodal diffuse large B-cell lymphoma. A total of 63 patients with primary nodal diffuse large B-cell lymphoma diagnosed in the Erciyes University Department of Hematology between 1990 and 2003 were included in the study. The median age of the patients was 55 years old (range 19-102 years old). The median follow-up period was 19 months (2-132 months). Histopathological sections were stained immunohistochemically and evaluated by light microscopy for Fas, bcl-2, and p53. Clinical and laboratory parameters including Fas, bcl-2, and p53 positivity, age, sex, performance status, clinical stage, presence of B symptoms, bone marrow involvement, extranodal involvement, and lactic dehydrogenase levels were evaluated to compare overall survival. Complete remission was obtained in 28 patients (44.4%) after first-line chemotherapy. Fas positivity, male gender, good performance status, clinical stage I-II, absence of B symptoms, normal lactic dehydrogenase value, and absence of bone marrow involvement were favorable prognostic factors for complete remission in statistical analysis. Multivariate analysis revealed that positive Fas expression and ECOG performance status were independent prognostic factors for overall survival. Also, Fas-positive patients had significantly prolonged progression-free survival. Immunohistochemical Fas positivity was a favorable prognostic factor for complete remission and overall and progression-free survival in primary nodal diffuse large B-cell lymphoma.
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PMID:Prognostic significance of Fas (CD95/APO-1) positivity in patients with primary nodal diffuse large B-cell lymphoma. 1701 88

Recently, mounting evidence has emerged to suggest that hyperbaric oxygenation (HBOT)-induced neuroprotection after experimental global ischemia and subarachnoid hemorrhage entails a decrease in the expression of hypoxia-inducible factor-1alpha (HIF-1alpha). Therefore, the purpose of this study was to test the hypothesis that oxygen-induced neuroprotection after neonatal hypoxia-ischemia involves alterations in the expression of HIF-1alpha. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% O(2) at 37 degrees C). Pups were then treated with HBOT (2.5 ATA) or normobaric oxygenation treatment (NBOT) for 2 h. The expression and phosphorylation status of HIF-1alpha was evaluated at intervals up to 24 h after the insult, as was the expression of glucose transporter (GLUT)-1, GLUT-3, lactate dehydrogenase (LDH), aldolase (Ald), and p53. The protein-protein interaction of HIF-1alpha and p53 was also examined. An elevated expression of HIF-1alpha, GLUT-1, GLUT-3, Ald, and LDH was observed after the insult. An increase in the dephosphorylated form of HIF-1alpha was followed by an increase in the association of HIF-1alpha with p53 and an increase in p53 levels. Both HBOT and NBOT reduced the elevated expression of HIF-1alpha and decreased its dephosphorylated form. Furthermore, both treatments promoted a transient increase in the expression of GLUT-1, GLUT-3, LDH, and Ald, while decreasing the HIF-1alpha-p53 interaction and decreasing the expression of p53. Therefore, the alteration of the HIF-1alpha phenotype by a single oxygen treatment may be one of the underlying mechanisms for the observed oxygen-induced neuroprotection seen when oxygen is administered after a neonatal hypoxic-ischemic insult.
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PMID:Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1alpha and its downstream target genes. 1672 20

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