Disease relevance of DEXI

• The increase in expression of DEXI found in emphysema patients' tissues may be owing to their known treatment with corticosteroids [1].
• EXPERIMENTAL DESIGN: PCDGF functions and signaling pathways in dexamethasone-induced apoptosis were studied using a representative dexamethasone-sensitive multiple myeloma cell line ARP-1 [2].
• Dexamethasone-induced adhesion in hepatoma cells: the role of plasminogen activator [3].
• Dexamethasone-induced damage to the antimicrobial activity of human macrophages in vitro parallels observations that glucocorticoids render laboratory animals susceptible to listeriosis and aspergillosis by damaging resident macrophages [4].
• Dexamethasone-induced bradycardia [5].

Psychiatry related information on DEXI

• Dexamethasone-induced increases in the plasma MHPG level were directly correlated with the severity of depressive symptoms and with postdexamethasone cortisol levels in the depressed patients [6].
• The experiments reported here tested the hypothesis that pre-treatment with oestrogen would also attenuate dexamethasone-induced neuronal damage as oestrogens have neuroprotective actions against a variety of insults and falling levels of oestrogen are associated with increased vulnerability to mood disorders [7].

High impact information on DEXI

• The glucocorticoid antagonist, RU-486, blocks the dexamethasone-induced changes but does not alter the basal rate of fibronectin production [8].
• We have studied cellular clusterin gene expression in vitro using three different models of PCD: (a) ultraviolet B (UV-B) irradiation of human U937, HeLa, and A431 cell lines, (b) in vitro aging of human peripheral blood neutrophils (PMNs), and (c) dexamethasone-induced cell death of the human lymphoblastoid cell line CEM-C7 [9].
• Furthermore, the dexamethasone-induced increase in insulin receptor mRNA levels was not blocked by pretreatment of cells with cycloheximide indicating that the glucocorticoid effect was independent of new protein synthesis [10].
• In addition, data from the thermolability assays correlated well with the lack at 45 degrees C of dexamethasone-induced decrease in in vitro [3H]thymidine incorporation into lymphocytes derived from both patients [11].
• Plasma 11-deoxycorticosterone and 18-hydroxy-11-dooxycorticosterone concentrations were normal Treatment with dexamethasone induced a return to normal of blood-pressure and plasma-potassium and an increase in plasma-renin activity and urinary aldosterone excretion [12].

Chemical compound and disease context of DEXI

• A novel carbohydrate-based therapeutic GCS-100 overcomes bortezomib resistance and enhances dexamethasone-induced apoptosis in multiple myeloma cells [13].
• 2-(8-Hydroxy-6-methoxy-1-oxo-1H-2-benzopyran-3-yl)propionic acid, a small molecule isocoumarin, potentiates dexamethasone-induced apoptosis of human multiple myeloma cells [14].
• Enforced expression of superoxide dismutase 2/manganese superoxide dismutase disrupts autocrine interleukin-6 stimulation in human multiple myeloma cells and enhances dexamethasone-induced apoptosis [15].
• Neither interleukin-6 nor insulin-like growth factor-I, which both induce multiple myeloma cell growth and abrogate dexamethasone-induced apoptosis, protect against FTY720-induced growth inhibition [16].
• Antioxidants, including bovine liver catalase, bovine erythrocyte CuZn-SOD, sodium selenite and Trolox, a water soluble vitamin E analogue, as well as hypoxia, inhibited dexamethasone-induced apoptosis [17].

Biological context of DEXI

• While inactive copies of DEXI are located within the repeats, we have now localized the active DEXI gene to 15q11-->q13 outside the PWS/AS deletion and Dexi to mouse chromosome 16, suggesting complex evolution of this genomic region in both species [18].
• Furthermore, these results suggest that inflammatory cytokine- and dexamethasone-induced IL-8 and ICAM-1, produced via a MAP kinase pathway, may serve as an important mediator of PDL immunoregulation involved in bone remodeling during orthodontic tooth movement [19].
• The human DEXI gene is intronless and the predicted open reading frame encodes a 95-residue acidic protein [1].
• The same result was obtained after dexamethasone-induced expression of p21-ras in stable NIH 3T3 transfectants containing either an activated Ha-ras oncogene or a normal N-ras proto-oncogene under control of the glucocorticoid-inducible MMTV promoter [20].
• The generation of prostaglandin E2 by A549 cells seems to be an important regulator of cell proliferation in vitro and the dexamethasone-induced suppression of proliferation in this model is attributable to eicosanoid inhibition caused by lipocortin 1 [21].

Anatomical context of DEXI

• These results identify a new molecular mechanism involved in the dexamethasone-induced regulation of NF-kappaB activity and T-cell activation [22].
• Expression of a third MHC class II molecule, HLA-DQ, was not induced on eosinophils by any of the cytokines alone, but in one of three donors tested, IL-3 plus dexamethasone induced high levels of expression [23].
• Finally, although binding of MM cells to bone marrow stromal cells augments MM cell growth and protects against dexamethasone-induced apoptosis, CT-32615 induced apoptosis even of adherent MM cells [24].
• Inhibition of caspases by peptide inhibitors blocked proteolysis of endogenous substrates and reduced nuclear condensation yet did not alter either dexamethasone-induced changes in clonogenicity or mitochondrial membrane potential [25].
• Filtration of unactivated CEM-C1 cytosol over Sephacryl S-300 generated a single peak of radioactivity for receptor complex with a calculated Stokes' radius of 55 to 59 A. Dexamethasone induced glutamine synthetase in CEM-C1 [26].

Associations of DEXI with chemical compounds

• DEXI mRNA was also upregulated 230% by dexamethasone treatment of A549 [1].
• The tetrapeptide inhibitor of CPP32(-like) proteases strongly inhibited Fas-mediated apoptosis, but only partially suppressed both C2-ceramide- and dexamethasone-induced apoptosis [27].
• Conversely, depressed patients, particularly those with psychotic features, showed a significant dexamethasone-induced increase in the plasma MHPG level and a blunting of the plasma HVA response relative to the normal controls [6].
• Actinomycin D, a potent inhibitor of transcription, abolished the dexamethasone-induced increase in beta AR mRNA, suggesting that the permissive hormone effect was exerted on gene transcription [28].
• It appears, however, that the degree of steroid action in vitro as well as the extent of spontaneous and dexamethasone-induced cell death may be related to the number of cells in the S phase of the cell cycle [29].

Physical interactions of DEXI

• The p53-mediated repression of dexamethasone-induced sgkGRE activity required both the DNA binding and transactivation functions of the p53 protein [30].
• In vitro spectral studies indicated that the formation of a P450 complex having absorbance maxima at 425 and 456 nm was time and concentration dependent; 27-60% of the total P450 was complexed in dexamethasone-induced rat liver microsomes after a 30-min incubation with 100 microM HIV protease inhibitors [31].
• Dexamethasone-induced fibronectin binding to HT-1080 cells was time dependent, dose dependent, and inhibited by cycloheximide [32].
• We have examined properties of glucocorticoid-receptor complexes which might account for dexamethasone induced alterations in the growth and morphology of melanoma target cells [33].

Regulatory relationships of DEXI

• Dexamethasone induced the proliferation and migration of HUVEC and activated eNOS [34].
• Expression of a GFP-TXNIP fusion protein was sufficient to induce apoptosis in WEHI7.2 cells, and repression of endogenous txnip by RNA interference inhibited dexamethasone-induced apoptosis in WEHI7.2 cells [35].
• Treatment of primary human monocytes with TGF-beta inhibited basal as well as dexamethasone-induced CD163 mRNA and protein expression [36].
• The dexamethasone-induced block of Grb2 recruitment was parallelled by changes in phosphorylation status and subcellular localization of lipocortin 1 (LC1) and an increase in the amount of the tyrosine phosphoprotein co-localized with EGF-R [37].
• Finally, overexpression of wild-type SAPKbeta was able to overcome the dexamethasone-induced block of TNF-alpha translation [38].

Other interactions of DEXI

• Identification of a functional link for the p53 tumor suppressor protein in dexamethasone-induced growth suppression [39].
• COL decreased the dexamethasone-induced luciferase expression in stably transfected cell line by 50%, whereas GR transactivation in transiently transfected cells was not affected by COL [40].
• Culture with TLR7- and TLR9-ligands saves HMCL from serum-deprivation or dexamethasone-induced apoptosis [41].
• PS-341 adds to the anti-MM activity of dexamethasone and overcomes IL-6-mediated protection against dexamethasone-induced apoptosis [42].
• Enzymatic activity and de novo protein synthesis of 3-methylcholanthrene-induced CYP1A2 and dexamethasone-induced CYP3A4 were also reduced to a much greater extent by oncostatin M than by other cytokines [43].

Analytical, diagnostic and therapeutic context of DEXI

• Measurements of cell membrane voltages obtained with intracellular microelectrodes indicated that the dexamethasone-induced rise in transepithelial voltage reflected a significant decrease (p less than 0.05) in apical membrane voltage, consistent with the induction of apical Na+ channels and the stimulation of electrogenic Na+ absorption [44].
• This result was confirmed by Northern blot analysis in multiple models of dexamethasone-induced apoptosis [35].
• In conclusion, dexamethasone induced a significant decrease in insulin sensitivity and a significant increase in insulin secretion during the oral glucose tolerance test [45].
• The dexamethasone-induced increase in leptin is dependent of body mass index, but not of insulin levels or insulin sensitivity, which suggests that the influence of dexamethasone on plasma leptin is not mediated by its influences on fasting insulin or insulin sensitivity [46].
• Conversely, myeloma cells recovered from cocultures had high survival rates and were resistant to dexamethasone-induced apoptosis [47].

References