Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to determine whether ornithine decarboxylase (ODC) has a role in mucosal repair during the first 24 h after stress-induced damage. Rats were fasted 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for 6 h. Animals were killed either immediately after the period of stress or at 2-h intervals up to 24 h thereafter. Gastric mucosal ODC increased significantly from 0 to 12 h and peaked 4 h after the 6-h stress period. By 24 h enzyme activity in the gastric mucosa was near normal. Macroscopic lesions were regularly produced after 6 h of stress. Histologically, stress caused extensive damage to the superficial epithelial cells, extending in some cases into the mucosa and beyond the basal lamina. However, after stress the mucosa recovered quickly, returning to near normal 24 h later. The decreases in mucosal content of DNA, RNA, and protein caused by stress also were restored and reached near-normal levels 24 h after stress. alpha-Difluoromethylornithine (DFMO), a specific inhibitor of ODC, not only inhibited the ODC activity but significantly delayed the recovery from injury as well. DFMO also prevented the restoration of DNA, RNA, and protein content of the gastric mucosa. In conclusion, stress-induced gastric mucosal lesions are accompanied by significant increases in ODC activity. The increased ODC is necessary for the normal repair of the mucosa.
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PMID:Role of ornithine decarboxylase in repair of gastric mucosal stress ulcers. 168 20

We recently found that stress increases gastric and duodenal ornithine decarboxylase (ODC) activity and damages both tissues. The current study investigated whether corticosterone induces ODC activity in gastric and duodenal mucosa in rats and compared plasma corticosterone levels after stress and treatment with corticosterone to determine whether this hormone mediated the effects of stress on the mucosa. Rats were fasted 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for 6 h. Stress markedly increased plasma corticosterone levels; the increase was 10.5 times control and lasted the duration of stress. The maximum increase was observed 1 h after a single injection of corticosterone (5 mg/kg sc) and represented 11.1 times control values. By 6 h, plasma corticosterone had returned to normal levels. A single injection of corticosterone had no effect on the gastric mucosa, but duodenal ODC was increased significantly from 4 to 8 h after injection, peaking at 6 h. Histological examination revealed no damage in either tissue. Administration of corticosterone three times daily for 3 days dramatically elevated ODC activity and produced significant microscopic damage. The surface epithelium of the stomach was disrupted, with many surface cells shed, and most villi were absent from the duodenal mucosa. Corticosterone also markedly decreased DNA and RNA content of both tissues. Inhibition of ODC with DL-alpha-difluoromethylornithine additionally decreased DNA, RNA, and protein content, exacerbating the damage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gastric and duodenal mucosal ornithine decarboxylase and damage after corticosterone. 169 1

The purpose of this study was to determine whether gastric and duodenal mucosal ornithine decarboxylase (ODC) activity increased during a period of ulcer-producing stress and whether changes in enzyme activity altered the severity of damage. Rats were fasted for 22 h, placed in a restraint cage, and immersed in water to the xiphoid process for different times lasting from 2 to 8 h. After 6 h, stress slightly increased gastric mucosal ODC and caused a sevenfold increase in duodenal mucosal ODC activity. Macroscopic ulcers developed in the oxyntic gland mucosa but not duodenal mucosa. Interestingly, however, after 6 h microscopic inspection showed an absence of most villi from the duodenum. DNA, RNA, and protein content of both tissues decreased over the time rats were exposed to stress. DL-alpha-Difluoromethylornithine (DFMO, a specific ODC inhibitor) prevented the increase in ODC in both tissues and increased the loss of DNA and RNA from duodenal mucosa. The degree of damage was not altered by DFMO in either tissue in response to 6 h of stress. These results show that 1) stress causes microscopic damage to the duodenum, 2) stress increases ODC in both gastric and duodenal mucosa, and 3) the inhibition of ODC during 6 h of stress does not alter the severity of damage.
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PMID:Induction of gastric and duodenal mucosal ornithine decarboxylase during stress. 247 32

Exposure of humans and rodents to radiofrequency (RF) cell phone fields has been reported to alter a number of stress- related parameters. To study this potential relationship in more detail, tube-restrained immobilized Fischer 344 rats were exposed in the near field in a dose-dependent manner to pulse-modulated (11 packets/s) digital cell phone microwave fields at 1.6 GHz in accordance with the Iridium protocol. Core body temperatures, plasma levels of the stress-induced hormones adrenocorticotrophic hormone (ACTH) and corticosterone, and brain levels of ornithine decarboxylase (Odc), Fos and Jun mRNAs were measured as potential markers of stress responses mediated by RF radiation. We tested the effects of the loose-tube immobilization with and without prior conditioning throughout a 2-h period (required for near-field head exposure to RF fields), on core body temperature, plasma ACTH and corticosteroids. Core body temperature increased transiently (+/-0.3 degrees C) during the initial 30 min of loose-tube restraint in conditioned animals. When conditioned/tube-trained animals were followed as a function of time after immobilization, both the ACTH and corticosterone levels were increased by nearly 10-fold. For example, within 2-3 min, ACTH increased to 83.2 +/- 31.0 pg/dl, compared to 28.1 +/- 7.7 pg/dl for cage controls, reaching a maximum at 15-30 min (254.6 +/- 46.8 pg/dl) before returning to near resting levels by 120 min (31.2 +/- 10.2 pg/dl). However, when non-tube-trained animals were submitted to loose-tube immobilization, these animals demonstrated significantly higher (3-10-fold greater) hormone levels at 120 min than their tube-trained counterparts (313.5 +/- 54.8 compared to 31.2 +/- 10.2 pg/dl; corticosterone, 12.2 +/- 6.2 microg/dl compared to 37.1 +/- 6.4 microg/dl). Hormone levels in exposed animals were also compared to those in swim-stressed animals. Swimming stress also resulted in marked elevation in both ACTH and corticosterone levels, which were 10-20 fold higher (541.8 compared to 27.2-59.1 pg/dl for ACTH) and 2-5 fold higher (45.7 compared to 8.4- 20.0 microg/dl for corticosteroids) than the cage control animals. Three time-averaged brain SAR levels of 0.16, 1.6 and 5 W/ kg were tested in a single 2-h RF-field exposure to the Iridium cell phone field. When RF-exposed and sham-exposed (immobilized) animals were compared, no differences were seen in core body temperature, corticosterone or ACTH that could be attributed to near-field RF radiation. Levels of Odc, Fos and Jun mRNA were also monitored in brains of animals exposed to the RF field for 2 h, and they showed no differences from sham-exposed (loose-tube immobilized) animals that were due to RF-field exposure. These data suggest that a significant stress response, indicated by a transient increase in core body temperature, ACTH and corticosterone, occurred in animals placed in even the mild loose-tube immobilization required for near-field RF exposure employed here and in our other studies. Failure to adequately characterize and control this immobilization response with appropriate cage control animals, as described previously, could significantly mask any potential effects mediated by the RF field on these and other stress-related parameters. We conclude that the pulse-modulated digital Iridium RF field at SARs up to 5 W/kg is incapable of altering these stress-related responses. This conclusion is further supported by our use of an RF-field exposure apparatus that minimized immobilization stress; the use of conditioned/tube-trained animals and the measurement of hormonal and molecular markers after 2 h RF-field exposure when the stress-mediated effects were complete further support our conclusion.
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PMID:Effect of immobilization and concurrent exposure to a pulse-modulated microwave field on core body temperature, plasma ACTH and corticosteroid, and brain ornithine decarboxylase, Fos and Jun mRNA. 1126 Jun 60

The molecular events associated with the development of adenocarcinoma of the oesophagus are not well understood. Gene expression associated with oesophageal adenocarcinoma was investigated using a cDNA array containing 1,176 human cancer-associated genes. Approximately 59% of the genes were expressed at detectable levels with 15 genes (1.3%) exhibiting differential (> 2.5-fold) expression in either normal oesophagus or adenocarcinoma tissue. Nine genes were up-regulated in oesophageal adenocarcinoma tissue (matrix metalloproteinase 11 (MMP11), ornithine decarboxylase (ODC), cytokeratins 8 and 18, integrin alpha 3 (ITGA3), integrin alpha 6 (ITGA6), BIGH3 (transforming growth factor beta-induced), beta-catenin and CDC25B (M-phase inducer phosphatase 2)). Six genes were down-regulated in adenocarcinoma tissue (cytokeratin 4, plasminogen activator inhibitor 2 (PAI-2), interleukin 1 receptor antagonist (IRAP), cytokeratin 13/15/17, MAD and retinoic acid receptor gamma 1 (RARG)). Many of these differentially expressed genes influence cell-cell adhesion, cell-extracellular matrix and composition, transcriptional activation and cell cycle progression and are likely to contribute to development of oesophageal adenocarcinoma.
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PMID:Transcriptional gene expression profiles of oesophageal adenocarcinoma and normal oesophageal tissues. 1268 Feb 8

Proteasomal protein degradation is a promising target for cancer therapy. Here, we developed a positron emission tomography (PET) technique based on the sodium-iodide symporter (NIS) gene fused with the carboxyl-terminal of ornithine decarboxylase (cODC) that noninvasively images cancer cells with inhibited proteasome activity. A retroviral vector was constructed in which the murine cODC degron was fused to the human NIS gene (NIS-cODC). Transiently transduced CT26 and HT29 colon cancer cells and stably expressing CT26/NIS-cODC cells were prepared. In cancer cells transiently transduced with NIS-cODC, NIS expression and transport activity was low at baseline, but NIS protein and 125I uptake was significantly increased by inhibition of proteasome activity with bortezomib. Stable CT26/NIS-cODC cells also showed increased cytosolic and membrane NIS by bortezomib, and four different stable clones displayed bortezomib dose-dependent stimulation of 125I and 99mTc-04- uptake. Importantly, bortezomib dose-dependently suppressed survival of CT26/NIS-cODC clones in a manner that closely correlated to the magnitudes of 125I and 99mTc-04- uptake. CT26/NIS-cODC tumors of bortezomib-treated mice demonstrated greater 124I uptake on PET images and increased NIS expression on tissue staining compared to vehicle-injected animals. NIS-cODC PET imaging may allow noninvasive quantitative monitoring of proteasome activity in cancer cells treated with bortezomib.
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PMID:Reporter PET Images Bortezomib Treatment-Mediated Suppression of Cancer Cell Proteasome Activity. 3011 45

We tested the hypothesis that tumor response to conventional bortezomib (BTZ) treatment is enhanced by targeted radiotherapy of resistant cancer stem cells (CSCs) that have characteristically poor proteasome function. This was accomplished by augmenting 131I uptake through expression of a sodium-iodide symporter (NIS) fusion protein that accumulates in cells with low proteasome activity. The NIS gene fused with the C-terminal of ornithine decarboxylase degron (NIS-cODC) was cloned. Stably expressing CT26/NIS-cODC cells and tumorsphere-derived CSCs were evaluated for NIS expression and radioiodine uptake. CT26/NIS-cODC cells implanted into mice underwent PET imaging, and tumor-bearing mice were treated with BTZ alone or with BTZ plus 131I. CT26/NIS-cODC cells accumulated NIS protein, which led to high radioiodine uptake when proteasome activity was inhibited or after enrichment for stemness. The cell population that survived BTZ treatment was enriched with CSCs that were susceptible to 131I treatment, which suppressed stemness features. Positron emission tomography and uptake measurements confirmed high 124I and 131I uptake of CT26/NIS-cODC CSCs implanted in living mice. In CT26/NIS-cODC tumor-bearing mice, whereas BTZ treatment modestly retarded tumor growth and increased stemness markers, combining 131I therapy suppressed stemness features and achieved greater antitumor effects. The NIS-cODC system offer radioiodine-targeted elimination of CSCs that are tolerant to proteasome inhibition therapy.
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PMID:Targeting poor proteasomal function with radioiodine eliminates CT26 colon cancer stem cells resistant to bortezomib therapy. 3286 72