Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have shown that lungs of adult mice exposed to >95% oxygen have increased terminal deoxyribonucleotidyltransferase dUTP nick end-label staining and accumulate p53, the expression of which increases in cells exposed to DNA-damaging agents. The present study was designed to determine whether hyperoxia also increased expression of the growth arrest and DNA damage (GADD) gene 45 and GADD153, which are induced by genotoxic stress through p53-dependent and -independent pathways. GADD proteins have been shown to inhibit proliferation and stimulate DNA repair and/or apoptosis. GADD45 and GADD153 mRNAs were not detected in lungs exposed to room air but were detected after 48 and 72 h of exposure to hyperoxia. In situ hybridization and immunohistochemistry revealed that hyperoxia increased GADD45 and GADD153 expression in the bronchiolar epithelium and GADD45 expression predominantly in alveolar cells that were morphologically consistent with type II cells. Hyperoxia also increased GADD expression in p53-deficient mice. Terminal deoxyribonucleotidyltransferase dUTP nick end-label staining of lung cells from p53 wild-type and p53-null mice exposed to hyperoxia for 48 h revealed that hyperoxia-induced DNA fragmentation was not modified by p53 deficiency. These studies are consistent with the hypothesis that hyperoxia-induced DNA fragmentation is associated with the expression of GADD genes that may participate in DNA repair and/or apoptosis.
Am J Physiol Lung Cell Mol Physiol 2000 Mar
PMID:p53-independent induction of GADD45 and GADD153 in mouse lungs exposed to hyperoxia. 1071 May 28

This study investigated N-methyl-D-aspartate (NMDA) mediated cell death and its possible regulation by calcium/calmodulin-dependent protein kinase II (CaMKII) in the adult rat retina. To investigate cell death, the terminal deoxyribonucleotidyltransferase (TdT)-mediated biotin-16-dUTP nick-end labelling (TUNEL) method was used to detect fragmented DNA in fixed tissue sections of rat retina. The TUNEL assay confirmed that apoptosis occurs in the inner nuclear layer (INL) and ganglion cell layer (GCL) following NMDA injection. The level of antibody binding to CaMKII-alpha, the activity of CaMKII, and the mRNA level for the alpha(B) subunit of CaMKII were found to be elevated for short time periods (30 min, 2 h) after a single intravitreal injection of NMDA. In contrast to this, there was a decrease in CaMKII activity and in the CaMKII-alpha(B) mRNA levels at longer time periods (24 h) following injection of NMDA. These effects were specific for the mRNA for the alpha(B) subunit, an alternatively spliced product of the CaMKII-alpha gene, that contains a nuclear localizing signal (NLS) known to target this protein to the nucleus. It is suggested that regulated expression of CaMKII-alpha(B) could be involved in the NMDA-mediated cell death in retinal neurons.
Brain Res Mol Brain Res 2000 Mar 29
PMID:Calcium/calmodulin-dependent protein kinase II containing a nuclear localizing signal is altered in retinal neurons exposed to N-methyl-D-aspartate. 1076

Here are described the effects of androgens, and other molecules known to bind to androgen receptors (AR), on MOP cells established from the human prostate cancer cell line LNCaP. MOP cells contained AR: 100000 binding sites/cell, K(D) for 5alpha dihydrotestosterone (DHT) 0.5 nM, size 110 kDa. The AR gene has the same repetition polymorphism in exon 1 and the T876A mutation in exon 8 as LNCaP. The proliferation of MOP cells in culture was repressed by the synthetic androgen 17beta-hydroxy-17-methyl-estra-4,9,11-trien-3-one (R 1881), the antiandrogen cyproterone acetate (CYPA), estradiol (E2), progesterone and the synthetic progestin promegestone: 17,21 dimethyl-19 nor-4,9 pregnandiene-3,20 dione (R 5020). The number of cells recovered after 7 days decreased to approximately 40% of controls. ED(70)s ranged between 50 pM for R 1881 to 50 nM for E2 and CYPA. Treatment with R 1881 decreased [3H]thymidine incorporation into DNA and increased dramatically the doubling time. R 1881, CYPA and E2 blocked the cell cycle between G1 and S phases and they induced apototosis as demonstrated by the increase of blebs on the plasma membrane, nuclear fragmentation, TdT-mediated dUTP nick end-labeling (TUNEL)-positive cells and internucleosomal DNA breaks. In athymic nude mice, testosterone enanthate prevented the growth of MOP tumors and, when tumors did develop, brought about regression. However, the tumors did not regress completely and finally escaped treatment. In conclusion, a variant of the LNCaP cell line has been established. With these cells it was possible to confirm that androgens paradoxically repress the growth of some prostate cancer cells both in culture and in vivo. In addition it is demonstrated in culture but not in vivo, for the first time to the authors' knowledge, that a synthetic androgen is able to induce apoptosis of cells established from human prostate carcinoma.
J Steroid Biochem Mol Biol
PMID:Inhibition of growth and induction of apoptosis by androgens of a variant of LNCaP cell line. 1107 Mar 52

Recently, we and others have shown that genetic and environmental changes that increase the load of yeast cells with reactive oxygen species (ROS) lead to a shortening of the life span of yeast mother cells. Deletions of yeast genes coding for the superoxide dismutases or the catalases, as well as changes in atmospheric oxygen concentration, considerably shortened the life span. The presence of the physiological antioxidant glutathione, on the other hand, increased the life span of yeast cells. Taken together, these results pointed to a role for oxygen in the yeast ageing process. Here, we show by staining with dihydrorhodamine that old yeast mother cells isolated by elutriation, but not young cells, contain ROS that are localized in the mitochondria. A relatively large proportion of the old mother cells shows phenotypic markers of yeast apoptosis, i.e. TUNEL (TdT-mediated dUTP nick end labelling) and annexin V staining. Although it has been shown previously that apoptosis in yeast can be induced by a cdc48 allele, by expressing pro-apoptotic human cDNAs or by stressing the cells with hydrogen peroxide, we are now showing a physiological role for apoptosis in unstressed but aged wild-type yeast mother cells.
Mol Microbiol 2001 Mar
PMID:Aged mother cells of Saccharomyces cerevisiae show markers of oxidative stress and apoptosis. 1125 34

The hSWI/SNF complex remodels the chromatin structure to modulate gene expression. The hSWI/SNF complex is a multiprotein complex with at least 10 different proteins in mammals. In this study, we identified the 45 kDa subunit of the hSWI/SNF complex as ArpN, an actin-related protein. ArpN has a 36% identity and 50% similarity with the human beta-actin, but cannot be classified into any known class of actin-related proteins. ArpN is exclusively localized within the nucleus and appears as the unbound, chromatin-associated, or nuclear matrix associated forms in the nucleus. In the chromatin immunoprecipitation (ChIP) assay, we found the associations of ArpN with the Ets-2 and c-mycP2 promoter regions in HeLa cells. The promoter regions of the hsp70, cyclophilin, beta-globin, TdT, and cd4 genes, however, were not associated with ArpN. The Ets-2 and c-mycP2 genes are expressed actively in HeLa cells, but beta-globin, TdT, and cd4 genes are inactive. The hsp70 and cyclophilin genes have a feature of stress-inducibility. These selective associations of ArpN with a subset of active genes support the proposition that the requirement of hSWI/SNF complex in gene activation is gene specific.
Mol Cells 2001 Feb 28
PMID:Identification of a nuclear protein ArpN as a component of human SWI/SNF complex and its selective association with a subset of active genes. 1126 25

We investigated the frequency of spontaneous apoptosis and expression of the Bcl-2 family of proteins during normal spermatogenesis in man. Testicular tissue with both normal morphology and DNA content was obtained from necro-donors and fixed in Bouin's solution. A TdT-mediated dUTP end-labelling method (TUNEL) was used for the detection of apoptotic cells. Expression of apoptosis regulatory Bcl-2 family proteins and of p53 and p21(Waf1) was assessed by immunohistochemistry. Germ cell apoptosis was detected in all testes and was mainly seen in primary spermatocytes and spermatids and in a few spermatogonia. Bcl-2 and Bak were preferentially expressed in the compartments of spermatocytes and differentiating spermatids, while Bcl-x was preferentially expressed in spermatogonia. Bax showed a preferential expression in nuclei of round spermatids, whereas Bad was only seen in the acrosome region of various stages of spermatids. Mcl-1 staining was weak without a particular pattern, whereas expression of Bcl-w, p53 and p21(Waf1) proteins was not detected by immunohistochemistry. The results show that spontaneous apoptosis occurs in all male germ cell compartments in humans. Bcl-2 family proteins are distributed preferentially within distinct germ cell compartments suggesting a specific role for these proteins in the processes of differentiation and maturation during human spermatogenesis.
Mol Hum Reprod 2001 May
PMID:Expression of Bcl-2 family proteins and spontaneous apoptosis in normal human testis. 1133 61

At present cadmium (Cd)-induced immunotoxicity and the mechanisms involved have not been fully elucidated. The main objective of the present study is to explore the apoptogenic property of Cd in primary cultured mouse thymocytes and its effect on cell surface marker expression and phenotypic changes. Cd-induced thymocyte apoptosis was determined by TdT-mediated dUTP nick end labeling (TUNEL) assay, DNA content/cell cycle analysis and DNA gel electrophoresis. The results showed that Cd was able to cause apoptosis in mouse thymocytes in a time- and dose-dependent manner. Moreover, different subsets of thymocytes possessed different susceptibility to the apoptotic effect of Cd, in the order of CD8+ > CD4- CD8- (double negative cells, DN) > CD4+ CD8+ (double positive cells, DP) > CD4+. Cd treatment also altered thymocyte surface marker expression, leading to evident phenotypic changes. Such changes were characterized by a decline in DP cells and a marked decrease in CD4+/CD8+ ratio, mainly due to a significant increase in CD8+ subsets. These observations help to obtain a better understanding of the immunotoxic and immunomodulatory effects of Cd.
Mol Cell Biochem 2001 Jun
PMID:Cadmium-induced apoptosis and phenotypic changes in mouse thymocytes. 1167 92

Prematurely born babies are often treated with glucocorticoids. We studied the consequences of an early postnatal and short dexamethasone treatment (0.1-0.01 microg/g, days 1-4) on lung development in rats, focusing on its influence on peaks of cell proliferation around day 4 and of programmed cell death at days 19-21. By morphological criteria, we observed a dexamethasone-induced premature maturation of the septa (day 4), followed by a transient septal immatureness and delayed alveolarization leading to complete rescue of the structural changes. The numbers of proliferating (anti-Ki67) and dying cells (TdT-mediated dUTP nick end labeling) were determined and compared with controls. In dexamethasone-treated animals, both the peak of cell proliferation and the peak of programmed cell death were reduced to baseline, whereas the expression of tissue transglutaminase (transglutaminase-C), another marker for postnatal lung maturation, was not significantly altered. We hypothesize that a short neonatal course of dexamethasone leads to severe but transient structural changes of the lung parenchyma and influences the balance between cell proliferation and cell death even in later stages of lung maturation.
Am J Physiol Lung Cell Mol Physiol 2002 Mar
PMID:Suppression of cell proliferation and programmed cell death by dexamethasone during postnatal lung development. 1183 41

Multiphoton laser scanning microscopy (MPLSM) is based on non-resonant simultaneous absorption of two or three near infrared (NIR) photons by a fluorophore in the subfemtoliter focal volume of a high numerical aperture (N.A. 1.3) objective. The higher penetration depth of NIR radiation enables optical sectioning across thick biological specimens and because of the absence of efficient single photon absorbers in the NIR spectral region of 700 to 1200 nm there is hardly any out-of-focus photodamage and photobleaching. Recent in vitro studies (14) have demonstrated that irradiation of supercoiled plasmid DNA with intense multiphoton NIR 810 nm of 140 fs pulse width, 76 MHz pulse repetition rate results in single strand breaks as a result of simultaneous absorption of three or more photons. Herein, we have investigated the influence of 800 nm NIR 170 fs laser pulses, 80 MHz pulse repetition frequency at mean powers of 2 to 20 mW on nuclear DNA of unlabelled PtK2 cells. In situ TdT-mediated dUTP-nick end labelling (TUNEL) revealed that cells exposed to the NIR irradiation above > or =5 mW mean laser power alone contained TUNEL-positive nuclei. The intensity of TUNEL fluorescence was relatively higher at increased mean NIR laser power. These results provide evidence that DNA strand breaks also occur in vivo when mammalian cells are exposed to high average power > or =5 mW NIR irradiation during MPLSM possibly due to multiphoton absorption process. Because intense DNA fragmentation is one of the hall marks of programmed cell death it is hypothesised that NIR induced cell death is by apoptosis.
Cell Mol Biol (Noisy-le-grand) 2001
PMID:Femtosecond near-infrared laser pulse induced strand breaks in mammalian cells. 1193 58

The kappa chain repertoire of individual IgD(+) human neonatal B cells was analyzed using a single cell PCR technique. A total of 104 productive and 90 non-productive VkappaJkappa rearrangements from three cord blood B cell samples were sequenced and compared to the adult IgM(+) peripheral B cell VkappaJkappa repertoire. All six Vkappa families were present in neonatal B cells, but the distribution was not random. In the non-productive repertoire Vkappa2 and Vkappa6 families were less frequent, Vkappa1 and Vkappa3 families were as frequent, and Vkappa4 and Vkappa5 families were more frequent than expected from random chance. Notably, the Vkappa2 family was negatively selected into the productive repertoire. In contrast, the Vkappa1 family was positively selected because of positive selection of three specific genes, O12/O2, L12a and L9. B3 (Vkappa4) and B2 (Vkappa5) were over-represented in the non-productive repertoire and then were expressed less frequently in the productive repertoire. In contrast, the Vkappa3 family gene, A27, was also over-represented in the non-productive repertoire but not further selected into the productive repertoire. Compared to the adult repertoire, junctional diversity was less marked because of a diminished influence of TdT activity, whereas the mean CDR3 length was comparable to that of normal adult B cells. Comparison of the distribution of Vkappa and Jkappa genes with those found in normal adult subjects suggested that there was less receptor editing in neonatal B cells. When neonatal CD5(+) B cells were compared with CD5(-) IgD(+) B cells, it was noted that the Vkappa gene A30 was used only in CD5(+) B cells in both the productive and non-productive repertoires. The results indicate that the usage of Vkappa genes by neonatal B cells is biased by both intrinsic molecular processes and selection. The evidence of selection indicates that the Vkappa repertoire is shaped by self antigens, since exposure to exogenous antigens is limited at the time of birth.
Mol Immunol 2002 Jun
PMID:The kappa gene repertoire of human neonatal B cells. 1204 78


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