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)

Ten archive cases of cardiac myxoma were evaluated for proliferative activity, metastatic potential and expression of oncogene/tumor suppressor gene products by means of PCNA, MIB1, nm23, p53, Bcl-2 and Rb-1 immunohistochemistry. The myxomas showed variable proliferative activity (PCNA 0-41%, average 12.6%, MIB1 0-13%, average 3.2%) contrasting with the absence of mitotic activity histologically. All the myxomas showed nm23 staining. None showed p53 reactivity. Eight cases were negative for Bcl-2 expression, with two cases giving weak cytoplasmic staining. Rb-1 reactivity showed a variable pattern (staining indices 0-86%) paralleling the cases' proliferative activity. The cardiac myxoma is interpreted as a weakly proliferative lesion with little metastatic potential and no modulation of oncogene/oncogene suppressor products. Whilst not excluding a neoplastic aetiology, the results are considered more in keeping with a reactive/hamartomatous process.
Int J Cardiol 1996 Dec 13
PMID:The nature of the cardiac myxoma. 902 8

Deoxyribonucleic acid (DNA) synthesis of mesenchymal cells in the diseased valve tissue of patients with rheumatic and non-rheumatic valve diseases were compared. Surgically resected mitral valves from eight rheumatic and eight non-rheumatic patients in their 40s were examined immunohistochemically to estimate the activity of the various mesenchymal cells by cell cycle analysis, using monoclonal antibodies to cyclin E, A, B1, p53, and b cl-2 after routine tissue fixation, paraffin embedding and sectioning. Cyclin B1-positive fibrocytes and fibroblasts of the spongiosa and fibrosa were observed in all non-rheumatic cases, whereas some lymphocytes in the perivascular area were cyclin B1-, p53- and b cl-2-positive in rheumatic cases. The distinct qualitative difference in the mesenchymal cells of valve tissue between rheumatic and non-rheumatic etiologies suggests a different mode of valve pathology.
J Cardiol 1997
PMID:[Variations in mesenchymal cell activity between rheumatic and non-rheumatic valve disease]. 921 Nov

Myocyte apoptosis increases with age in Fischer 344 rats, but the multiple molecular events implicated in this phenomenon remain to be identified. Several defects involving Ca2+ homeostasis, pH, and the expression of p53 and genes of the Bcl-2 protein family may contribute to the activation of myocyte death. Therefore, changes in intracellular pH, cytosolic Ca2+, DNase I and DNase II were measured in myocytes isolated by enzymatic digestion from rats of different ages. Moreover, the expression of p53, Bcl-2 and Bax in these cells was determined. Measurements of intracellular pH by BCECF fluorescence at 3, 12 and 24 months showed that this parameter did not change with age: 3 months, 7.20+/-0.05; 12 months, 7.21+/-0.07; 24 months, 7.18+/-0.09. In contrast, diastolic Ca2+ determined by the Fura 2-AM method increased progressively from 99.8+/-1.9 nm at 3 months to 136.3+/-9.6 nm at 24 months (P<0.001). Concurrently, DNase I activity evaluated by plasmid digestion assay in myocytes increased 3.2-fold from 3 to 24 months (P<0.02). Conversely, pH-dependent-DNase II remained essentially constant with age. Western blotting performed on ventricular myocytes did not detect significant changes in p53, Bax and Bcl-2 proteins with age. Similarly, immunocytochemically, the fraction of myocytes labeled by p53, Bax and Bcl-2 did not change from 3 to 24 months. In conclusion, myocyte aging is characterized by an increase in diastolic calcium which may activate DNase I triggering apoptosis, independently from the expression of p53, Bax and Bcl-2 in the cells.
J Mol Cell Cardiol 1998 Mar
PMID:Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. 951 29

Programmed cell death or apoptosis is an active physiological process that permits the removal of unwanted or damaged cells from the body through an intrinsic cell-suicide program. Apoptosis is characterized by condensation of the nucleus and cytoplasm without loss of membrane integrity. The occurrence of apoptosis in the vasculature and myocardium has recently been described. Inappropriate loss of myocardial cells is suggested to contribute to conduction defects and ventricular remodelling after injury. The molecular mechanisms that regulate programmed cell death in cardiac muscle cells are poorly defined. However, recent evidence has suggested that specific genes can either provoke or prevent apoptosis. In this regard, the tumour suppressor protein p53 has been proposed to mediate apoptosis, while the Bcl-2 protein prevents it. Prevention of apoptosis in the heart is potentially of significant therapeutic value given the limited capacity of the heart to repair itself after injury. This study determined that the expression of p53 in ventricular myocytes is sufficient to trigger apoptosis. Moreover, p53 results in a significant increase in the expression of the death-promoting protein Bax. Importantly, the antiapoptotic factor Bcl-2 is sufficient to prevent p53-mediated apoptosis and p53-dependent transcription of Bax in ventricular myocytes. The data substantiate a role for p53 and Bcl-2 as crucial regulators of apoptosis in the heart.
Can J Cardiol 1998 Mar
PMID:Regulators of apoptosis in the heart: a matter of life and death. 955 Oct 35

The micropathology of chronic Chagas' myocarditis reveals foci of myocardial cell loss associated with an inflammatory infiltrate composed predominantly of lymphomononuclear cells and interstitial fibrosis. The loss of myocardial cells, a devastating phenomenon in this cardiopathy, has been classically attributed to necrosis. In the present study we examined whether the loss of myocardial cells in human chronic Chagas' heart disease could result from cell death by apoptosis. A total of 11 cases of chronic chagasic myocarditis were studied: four hearts were obtained at autopsy within 8 h after death and seven endomyocardial biopsies were taken from chagasic patients with an arrhythmogenic form of the disease. The coronary arteries of all chagasic cases showed no obstructive lesions. The diagnosis of Chagas' disease was based on previously established criteria. Five cases were selected as controls: three hearts were obtained at autopsy within 8 h after death and two endomyocardial biopsies were taken from nonchagasic patients with normal myocardium morphology. As positive controls we used cardiac muscles of myocardial infarction and rat mammary glands on the fourth day after weaning. The TUNEL method was used to identify apoptotic cells in the myocardium. The expression of p53 protein, which directly or indirectly triggers apoptosis, was evaluated using immunohistochemical technique. A few apoptotic cells were stained in chronic chagasic hearts, both biopsy and autopsy cases. However, the stained nuclei were restricted to the mononuclear infiltrate accounting for about 0.5% of the mononuclear cells in the infiltrate. In contrast, the nuclei of cardiomyocytes in both regions bordering on and distant from the microfoci of myocardial cell loss were not stained by the TUNEL method. Moreover, the expression of the protein p53 in cardiomyocytes in chagasic hearts was absent. The results of the present study demonstrating negative in situ labeling of fragmented DNA associated with absence of expression of p53 provide support to the hypothesis that apoptosis is not the mechanism of cell death in chronic chagasic myocarditis. This reinforces the general opinion that the loss of cardiac muscle fibers in chagasic cardiopathy is produced by necrosis. On the other hand, the present results give support to the concept that apoptosis probably play a role in the clearing of lymphomononuclear cells in the inflammatory infiltrate in chronic chagasic myocarditis.
Int J Cardiol 1999 Mar 15
PMID:Is apoptosis a mechanism of cell death of cardiomyocytes in chronic chagasic myocarditis? 1021 85

Factors produced by the heart are accumulated at high concentrations in pericardial fluid. We recently reported that pericardial fluid from patients with ischemic heart disease induces apoptosis in an F2 cell line. To characterize factors in pericardial fluid from patients with ischemic heart disease, we investigated signaling pathways by which this pericardial fluid induces apoptosis in cardiac myocytes. Pericardial fluid from patients with ischemic heart disease markedly increased the percentage of TUNEL-positive myocytes compared with fetal bovine serum. Apoptosis was also confirmed by ladder formation and morphologic features. Apoptosis mediated by this pericardial fluid occurs as readily in cardiac myocytes prepared from neonatal mice nullizygous for p53 as in wild-type littermates. This indicates that p53 is not required for this process. We have found that pericardial fluid from ischemic heart disease elicits a robust increase in phosphorylation of p38 mitogen-activated protein kinase. Specific inhibition of the p38 mitogen-activated protein kinase pathway with SB 203580 almost completely blocked apoptosis mediated by pericardial fluid from ischemic heart disease. Activation of p38 mitogen-activated protein kinase is caused by cellular stress, including oxidants. We have also found that anti-oxidant catalase inhibited pericardial fluid-induced activation of p38 mitogen-activated protein kinase and apoptosis. These findings demonstrate that myocardial cell apoptosis induced by pericardial fluid from patients with ischemic heart disease is mediated by an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway. A possible application of SB 203580 to preserve cardiac function in patients with ischemic heart disease should be discussed.
J Mol Cell Cardiol 2001 Mar
PMID:Pericardial fluid from patients with ischemic heart disease induces myocardial cell apoptotis via an oxidant stress-sensitive p38 mitogen-activated protein kinase pathway. 1118 Oct 11

Targeted expression of the SV40 large T-antigen oncoprotein (T-Ag) induces cardiomyocyte proliferation in the atria and ventricles of transgenic mice. Previous studies have identified the p53 tumor suppressor, p107 (a homologue of the retinoblastoma tumor suppressor), and p193 (a novel BH3 only proapoptosis protein) as prominent TAg binding proteins in cardiomyocyte cell lines derived from these transgenic mice. To further explore the significance of these protein-protein interactions in the regulation of cardiomyocyte proliferation, a transgene comprising the human atrial natriuretic factor (ANF) promoter and sequences encoding a mutant T-Ag lacking the p53 binding domain was generated. Repeated micro-injection of this DNA gave rise to genetically mosaic animals with minimal transgene content, suggesting that widespread cardiac expression of mutant T-Ag was deleterious. This notion was supported by the observation that the transgene was selectively lost from the cardiac myocytes (but not the cardiac fibroblasts) in the mosaic animals. Crosses between the mosaic mice and animals expressing a cardiac restricted dominant negative p53 resulted in transgene transmission with ensuing overt cardiac tumorigenesis. Transfection of the mutant T-Ag in embryonic stem (ES) cell-derived cardiomyocytes resulted in wide-spread cell death with characteristics typical of apoptosis. Co-transfection with a dominant negative p53 transgene rescued mutant TAg-induced cell death in the ES-derived cardiomyocyte cultures, resulting in a marked proliferative response similar to that seen in vivo with the rescued transgenic mouse study. These results indicate that T-Ag expression in the absence of p53 functional abrogation results in cardiomyocyte death.
J Mol Cell Cardiol 2001 Aug
PMID:Functional abrogation of p53 is required for T-Ag induced proliferation in cardiomyocytes. 1144 30

The tumor suppressor p53 is known to regulate gene transcription and apoptosis in mammalian cells. In the present study we ascertain whether these events are mutually dependent and obligatorily linked for induction of apoptosis of ventricular myocytes. Adenovirus mediated gene delivery of wild p53 (p53WT) or a mutant form of p53 (p53MT) defective for gene transcription to ventricular myocytes was confirmed by Western blot analysis. A significant increase in the p53 dependent genes Bax and MDM2 was observed with p53WT but not p53MT. Nuclear DNA visualized by agarose gel electrophoresis revealed nucleosomal DNA laddering in the presence of either p53 protein. Apoptosis was substantiated by Hoechst 33258 nuclear staining. Perturbations to mitochondria consistent with the mitochondrial death pathway, including loss of mitochondrial transmembrane potential Delta(psi)m and cytochrome c release were observed with p53WT and p53MT. An increase in caspase 3-like activity was noted with either p53WT or p53MT protein that was suppressed by the caspase 3 inhibitor Ac-DEVD-CHO. To our knowledge the experiments described here provide the first indication that p53 activates the mitochondrial death pathway and provokes apoptosis of ventricular myocytes independent of DNA binding and de novo gene activation.
J Mol Cell Cardiol 2001 Aug
PMID:p53 activates the mitochondrial death pathway and apoptosis of ventricular myocytes independent of de novo gene transcription. 1144 32

Calsequestrin is a sarcoplasmic reticulum protein, which plays a predominant role in diastolic Ca2+-storage in the mammalian heart. The present study was designed to define the gene structure, developmental and tissue specific expression of the murine, cardiac isoform of calsequestrin. Two sets of genomic libraries (lambda phage and PAC) were screened using the mouse cardiac calsequestrin cDNA, and several overlapping clones were isolated. These clones were characterized using restriction enzyme digestion, Southern blotting and partial sequencing. The cardiac calsequestrin gene consists of 11 exons and its 5' flanking region is characterized by the presence of a TATA-like box, muscle specific promoter elements such as 7 E-boxes, 1 MEF-2, 1 MCBF and 1 Repeat (musS) motifs, as well as several muscle non-specific transcriptional elements (AP-2A, NRE1, NRE2, p53, Spel and TFI-IIA). Expression of the cardiac isoform of calsequestrin was first detected on day 11 pre-birth and approached adult levels by day 4 post-birth. Expression of cardiac calsequestrin was also detected in adult fast-twitch skeletal muscle, thyroid, testis and epididymis tissues. This genomic characterization of cardiac calsequestrin may form the basis for further evaluation of its regulatory role in Ca2+ homeostasis and contractility in the murine heart.
Basic Res Cardiol 2001 Nov
PMID:Structure and expression of the mouse cardiac calsequestrin gene. 1177 83

c-Myc and p53 are two proteins that have critical roles in the regulation of apoptosis and the cell cycle. The authors review how these two proteins are thought to control the opposing events of proliferation and apoptosis and examine whether their well-documented biological roles in tumorigenesis can be applied to the vascular system.
Cardiol Clin 2001 Feb
PMID:Apoptotic proteins. p53 and c-myc related pathways. 1178 15


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