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)

Folate depletion and aging are risk factors for colorectal cancer. We investigated the effects of folate status and aging on gene expression in the rat colon. Young (weanling) and older (12 month) rats were fed folic acid depleted (0 mg/kg) and supplemented (8 mg/kg) diets for 20 weeks. Gene expression was measured in colonic mucosal scrapings (n = 3 per group) using oligonucleotide arrays (Affymetrix U34A). Folate depletion induced the up-regulation of immune-related genes, urokinase and inducible nitric oxide synthase and the down-regulation of adhesion molecules (protocadherin-4, nidogen and integrin alphaV) and vascular endothelial growth factor in young rats. The abbreviated response to depletion in old rats (62 changes versus 136 in the young) included up-regulation of caspase-2 and deleted in colon cancer. Gene expression changes due to aging were more abundant in folate depleted than supplemented rats (38 versus 119 genes, respectively). In folate-deficient rats, aging induced the down-regulation of immune-related genes, urokinase, p53, insulin-like growth factor binding protein-3 and vav-1 oncogene. In folate supplemented rats, aging induced the down-regulation of vascular endothelial growth factor and caspase-2. Lower expression of adhesion molecules and higher expression of urokinase with folate depletion in young rats may indicate that cell detachment and migration, cancer-related processes, may be modulated by folate status. An age-related decline in p53 and IGF-BP3 expression was only observed in folate depleted animals, indicating that folate supplementation may reduce the risk for age-associated cancers by suppressing deleterious changes in the expression of certain genes.
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PMID:Effects of dietary folate and aging on gene expression in the colonic mucosa of rats: implications for carcinogenesis. 1297 65

To develop an efficient animal model for colitis-related carcinogenesis, male Crj: CD-1 (ICR) mice were given a single intraperitoneal administration (10 mg/kg body weight) of a genotoxic colonic carcinogen, azoxymethane (AOM), and a 1-week oral exposure (2% in drinking water) to a non-genotoxic carcinogen, dextran sodium sulfate (DSS), under various protocols. At week 20, colonic neoplasms (adenocarcinomas, 100% incidence with 5.60 +/- 2.42 multiplicity; and adenomas, 38% incidence with 0.20 +/- 0.40 multiplicity) with dysplastic lesions developed in mice treated with AOM followed by DSS. Protocols in which AOM was given during or after DSS administration induced a few tubular adenomas or no tumors in the colon. Immunohistochemical investigation of such dysplasias and neoplasms revealed that all lesions were positive for beta-catenin, cyclooxygenase-2 and inducible nitric oxide synthase, but did not show p53 immunoreactivity. The results indicate that 1-week administration of 2% DSS after initiation with a low dose of AOM exerts a powerful tumor-promoting activity in colon carcinogenesis in male ICR mice, and may provide a novel mouse model for investigating colitis-related colon carcinogenesis and for identifying xenobiotics with modifying effects.
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PMID:A novel inflammation-related mouse colon carcinogenesis model induced by azoxymethane and dextran sodium sulfate. 1461 73

Since the first detection of aberrant crypt foci (ACF) in carcinogen-treated mice, there have been numerous studies focusing on these microscopically visible lesions both in rodents and in humans. ACF have been generally accepted as precancerous lesions in regard to histopathological characteristics, biochemical and immunohistochemical alterations, and genetic and epigenetic alterations. ACF show variable histological features, ranging from hyperplasia to dysplasia. ACF in human colon are more frequently located in the distal parts than in the proximal parts, which is in accordance with those in colorectal cancer (CRC). The immunohistochemical expressions of carcinoembryonic antigen (CEA), beta-catenin, placental cadherin (P-cadherin), epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and P16INK4a are found to be altered. Genetic mutations of K-ras, APC and p53, and the epigenetic alterations of CpG island methylation of ACF have also been demonstrated. Genomic instabilities due to the defect of mismatch repair (MMR) system are detectable in ACF. Two hypotheses have been proposed. One is the "dysplasia ACF-adenoma-carcinoma sequence", the other is "heteroplastic ACF-adenoma-carcinoma sequence". The malignant potential of ACF, especially dysplastic ACF, makes it necessary to reveal the nature of these lesions, and to prevent CRC from the earliest possible stage. The technique of magnifying chromoscope makes it possible to detect "in vivo" ACF, which is beneficial to colon cancer research, identifying high-risk populations for CRC, and developing preventive procedures.
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PMID:Aberrant crypt foci as microscopic precursors of colorectal cancer. 1466 4

Sodium cyanide (NaCN)-induced chemical hypoxia is known to increase intracellular free calcium concentration and reduce cell survival, but its effect on gene expression has not been studied. In this study, we designed primers to conduct a rapid and reliable assay for the expression of mRNA of inducible nitric oxide synthase (iNOs), tumor suppressor protein p53, Bcl-2, heat shock protein 70 (HSP-70), and beta-actin in human intestinal epithelial T84 cells and Jurkat T cells. NaCN-induced chemical hypoxia increased iNOs and HSP-70 mRNA in both types of cells, whereas p53 and Bcl-2 mRNA were singularly induced in T84 cells and Jurkat T cells, respectively. In both cell types, treatment of hypoxic cells with a reversible selective iNOs inhibitor, Now-nitro-L-arginine (LNNA), blocked iNOs, Bcl-2, and HSP-70 mRNA, but increased p53. The NaCN-induced hypoxia was also found to increase caspase-3 cellular activity in both cell types. Treatment with LNNA alone decreased the basal caspase-3 cellular activity. A prior treatment of LNNA significantly inhibited the NaCN-induced increase in the cellular activity of this apoptotic enzyme. This is the first report to show that NaCN-induced chemical hypoxia alters both stress-related gene expression and caspase-3 cellular activity and can be regulated by the iNOs inhibitor LNNA. Since NaCN has been included in the 'National chemical terrorism threat' list, by the US Department of Defense, our studies provide useful insight in the development of molecular sensors to detect early exposure to this chemical terrorism threat.
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PMID:NaCN-induced chemical hypoxia is associated with altered gene expression. 1467

There has been a recent upsurge of interest in radiation-induced bystander effects. Previously we reported that the accumulation of inducible nitric oxide (NO) synthase (iNOS) was induced only in human glioblastoma mutant (m) p53 cells by acute irradiation with X-rays, suggesting a suppression of iNOS induction after acute irradiation with X-rays in wtp53 cells. NO secreted from the irradiated mp53 cells induced the accumulation of p53 in unirradiated wtp53 cells. The radiosensitivity of wtp53 cells was reduced by exposure to the conditioned medium from irradiated mp53 cells, suggesting that NO is an initiator of radiation-induced bystander effects. In the present study, we found that the accumulation of iNOS in wtp53 cells was induced by chronic irradiation with gamma-rays followed by acute irradiation with X-rays, but not by each one. It is suggested that the accumulation of iNOS may be due to the depression of acute irradiation-induced p53 functions by pre-chronic irradiation. We found that chronic irradiation with gamma-rays did not inhibit the accumulation of p53 after exposure to the conditioned medium from the irradiated mp53 cells. However, the decay of accumulated p53 was stimulated by chronic irradiation with gamma-rays. At the same time, the accumulation of Hdm2 was observed; suggesting that chronic irradiation with gamma-rays may stimulate the degradation of p53 accumulated by NO-mediated bystander effects.
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PMID:Indirect influences of radiation on unirradiated cells through irradiated cells. 1467 5

Our goal has been to investigate the expression and correlated significance of inducible nitric oxide synthase (iNOS) and P53, Bax in benign and malignant gallbladder diseases. We detected the expression of iNOS, P53 and Bax in the gallbladder wall by SP immunohistochemistry in 16 cases of chronic cholecystitis, 11 cases of chronic cholecystitis with adenomyoma and 24 cases of gallbladder adenocarcinoma. The percentage of positively marked tumor cells was counted under microscope and the intensity of immunoreactivity was graded. SPSS10.0 statistical software was applied for statistical analysis. In this study, we found that: (1) Both benign and malignant diseased gallbladder wall expressed iNOS and Bax. Compared to benign diseased gallbladders, their expression in adenocarcinoma was decreased (p < 0.05), P53 was expressed strongly only in nuclei of adenocarcinoma cells of some cases. (2) In benign and malignant diseased gallbladders, iNOS expression was related positively to Bax (p < 0.01), the expression of P53 and Bax had a negative relationship (p < 0.01). The results suggested that both chronic cholecystitis and chronic cholecystitis with adenomyoma carry the risk of becoming malignant, especially the latter. NO is an important mediated molecule in cancer, there are intimate relationships between gallbladder cancer and apoptosis.
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PMID:Correlated expression of inducible nitric oxide synthase and P53, Bax in benign and malignant diseased gallbladder. 1470

The gene expressions for macrophage chemoattractant protein-1 (MCP-1), interleukin (IL)-1 beta, IL-2 and p53 were examined by semi-quantitative RT-PCR in corpora lutea (CL) of rabbits during spontaneous luteolysis at days 13, 15, 18 and 22 of pseudopregnancy. In the same luteal tissue, total activity of nitric oxide (NO) synthase (NOS) and genes for both endothelial (eNOS) and inducible (iNOS) isoforms were also analysed. From day 13 to 15, MCP-1 and IL-1 beta mRNA levels rose (P < or = 0.01) almost 2-fold, and the transcript for p53 almost 8-fold, but then all dropped (P < or = 0.05) from day 18 onward. IL-2 mRNA abundance was higher (P < or = 0.01) on day 13 and then gradually declined. During luteolysis, eNOS mRNA decreased 40% (P < or = 0.05) by day 15, but thereafter remained unchanged, while iNOS mRNA was barely detectable and did not show any clear age-related pattern throughout the late luteal stages. Total NOS activity progressively increased (P < or = 0.01) from day 13 to 18 of pseudopregnancy and then dropped to the lowest (P < or = 0.01) levels on day 22. Luteal progesterone content also declined during CL regression from 411 to 17 pg/mg found on days 13 and 22 respectively, in parallel with the decrease in blood progesterone concentrations. These data further support a physiological role of NO as modulator of luteal demise in rabbits. Locally, luteal cytokines may be involved in the up-regulation of NOS activity, while downstream NO may inhibit steroroidogenesis and induce expression of p53 gene after removal of the protective action of progesterone.
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PMID:Expression patterns of cytokines, p53 and nitric oxide synthase isoenzymes in corpora lutea of pseudopregnant rabbits during spontaneous luteolysis. 1505 89

Helicobacter pylori colonizes the human stomach and causes gastric disease. The resulting gastric damage is a multi-step process involving several molecular factors and different target cells. Th1 cytokines released by neutrophils and lymphoid cells that infiltrate gastric mucosa, nitric oxide production and inducible nitric oxide synthase (iNOS) are associated with immune activation and tissue injury. Many other molecular processes such as apoptosis, as well as angiogenic factors and integrins, are involved in H. pylori pathogenesis. We used cancer gastric cells AGS and MKN as experimental models to evaluate apoptotic rates, iNOS gene expression with and without the presence of interferon-gamma (IFN-gamma), placenta growth factor gene expression and alphav modulation. Our results show that AGS cells stimulated with H. pylori underwent apoptosis. Moreover, the addition of IFN-gamma caused a further increase in iNOS gene expression and in the apoptotic rates. We also found early modulation in PlGF and alphav expression, and noted that p53 and bax gene expression was involved in the apoptotic process. Taken together, these findings demonstrate that H. pylori employs a series of mechanisms to avoid the host defense and cause gastric mucosa damage. One H. pylori pathogenic mechanism for causing gastric damage is the induction of iNOS-dependent apoptosis that is strongly enhanced by IFN-gamma. Thus, data obtained indicate that Th1 cytokines such as IFN-gamma, via modulation of iNOS gene expression, may contribute to an increase in the pathogenicity of H. pylori infections.
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PMID:Interferon-gamma cooperates with Helicobacter pylori to induce iNOS-related apoptosis in AGS gastric adenocarcinoma cells. 1514 23

Curcumin (diferuloylmethane) inhibits tumour cell growth by inducing apoptosis in many tumour types, including melanoma, via complex and ill-defined pathways. Recent studies have shown that curcumin is both a nitric oxide scavenger and an inhibitor of inducible nitric oxide synthase (iNOS) expression, low levels of which correlate with antiapoptotic function and poor survival and which may be regulated by inhibition of nuclear factor-kappaB (NFkappaB) activation. To elucidate the mechanisms by which curcumin inhibits melanoma proliferation, we tested the in vitro effects of curcumin on specific cell cycle pathways and melanoma cell survival, including NFkappaB activation. Curcumin induced melanoma cell apoptosis and cell cycle arrest, which is associated with the downregulation of NFkappaB activation, iNOS and DNA-dependent protein kinase catalytic subunit expression, and upregulation of p53, p21(Cip1), p27(Kip1) and checkpoint kinase 2. Curcumin also downregulated constitutive iNOS activity in melanoma cells. Our results demonstrate that curcumin arrested cell growth at the G(2)/M phase and induced apoptosis in human melanoma cells by inhibiting NFkappaB activation and thus depletion of endogenous nitric oxide. Therefore, curcumin should be considered further as a potential therapy for patients with melanoma.
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PMID:Inhibition of nuclear factor-kappaB and nitric oxide by curcumin induces G2/M cell cycle arrest and apoptosis in human melanoma cells. 1517 84

In situ hybridization, immunohistochemistry, and TUNEL staining were applied to renal biopsy specimens of immunoglobulin A nephropathy (IgAN) patients to determine the expression of nitric oxide synthase (iNOS) (mRNA and protein), p53, and their potential roles in renal cell apoptosis in relation to the development of pathologic lesions. Fifty-one cases were categorized into four subgroups (A-D) according to the presence of progressive histopathological features. A cell type-specific and differential overexpression of iNOS mRNA and protein was demonstrated in glomerular cells in subgroups (A-C) and was found to correlate well with the upregulation of p53 protein by glomerular endothelium and epithelium in early- and advanced-stage disease. In the tubulointerstitium, induction of iNOS products was evident in damaged tubules in late-stage disease, in parallel with the upregulation of p53 protein levels in these tubules. Increased TUNEL staining observed in glomeruli with progressive lesions and tubules with degenerative changes positively correlated with the expression levels of iNOS and p53 in glomerular endothelium, epithelium, and their overexpression in damaged tubules. Clinicopathologic correlations demonstrated that induction of iNOS products in renal cells was associated with indices of poor renal prognosis in human IgAN. The coupled induction of iNOS and p53 upregulation in intrinsic renal cells of IgAN may be linked with both pro- and anti-apoptotic activities, thus playing an important role in mediating progressive renal injury and determining renal outcome in human IgAN.
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PMID:Coupled induction of iNOS and p53 upregulation in renal resident cells may be linked with apoptotic activity in the pathogenesis of progressive IgA nephropathy. 1528 93


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