Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroform is a drinking water contaminant that has been demonstrated to be carcinogenic to mice and rats resulting in an increased incidence of liver and kidney tumors, respectively. The mechanism of chloroform carcinogenicity might be by tumor initiation and/or promotion. Since induction of ornithine decarboxylase (ODC) activity has been proposed as a molecular marker for tumor promoters, we have investigated the effect of chloroform on ODC activity in rats. Chloroform induced a dose-dependent increase of hepatic ODC with an apparent threshold at 100 mg/kg body weight. Female rats were two to four times more susceptible to to chloroform. Upon daily dosing of chloroform for 7 days the liver became less susceptible, with the last dose of chloroform resulting in only 10% of the activity observed after a single dose. Nuclear RNA polymerase I activity was also induced by chloroform. Chloroform, rather than increasing the activity of renal ODC, resulted in a 35% reduction. The induction by chloroform of hepatic ODC activity might be associated with regenerative hyperplasia while the renal carcinogenicity of chloroform could not be demonstrated to be associated with ODC induction.
...
PMID:Chloroform induction of ornithine decarboxylase activity in rats. 715 57

Ornithine decarboxylase (ODC) plays an important role in cell proliferation. Its expression is tightly regulated at the mRNA and protein levels and is found to be deregulated in various malignancies. The rapid and dramatic induction of cellular ODC mRNA upon serum addition raised the possibility that a transcriptional attenuation mechanism may be involved in the regulation of ODC gene expression. Using transcription in HeLa nuclear extract and isolated transcription complexes, we have identified two sites of transcription arrest downstream to the transcription start site: Attenuator 1 (Att.1) located at +220, near two repeats of a USF/Myc-Max binding consensus sequence and attenuator 2 (Att.2) located at +1590 near a long stretch of T-residues. The two attenuators exhibit distinct properties as revealed by elongation of briefly initiated and partially purified transcription complexes: Att.1 serves as a transient pause site while arrest at Att.2 is more prolonged. The arrest at both attenuators is modulated by the general elongation factor TFIIS. In a promoter independent transcription system, using partially purified RNA polymerase II, only Att.2 was recognized efficiently. This suggests that the recognition of Att.2 is an intrinsic property of the polymerase while Att.1 recognition has to be facilitated by an auxiliary factor/s.
...
PMID:Transcription elongation of the murine ornithine decarboxylase (ODC) gene is regulated in vitro at two downstream elements by different attenuation mechanisms. 753 63

We have generated a transgenic mouse line harbouring the functional (chromosome-1-derived) human spermidine synthase (EC 2.5.1.16) gene in their genome. The transgenic animals expressed the human gene-derived mRNA, as revealed by reverse-transcriptase/PCR analysis, in all tissues studied and displayed tissue spermidine synthase activity that was 2-6 times that in their syngenic littermates. The elevated spermidine synthase activity, however, had virtually no effect on tissue putrescine, spermidine or spermine levels. The view that the accumulation of spermidine and spermine is possibly controlled by S-adenosylmethionine decarboxylase was further supported by the finding that tissue spermidine and spermine contents also remained practically normal in hybrid transgenic mice over-expressing both human ornithine decarboxylase and spermidine synthase genes.
...
PMID:Transgenic mice over-expressing the human spermidine synthase gene. 834 31

Caerulein-induced pancreatitis (CIP) in rats is characterized by oedema and cell necrosis followed by spontaneous regeneration. The ras protein as well as ornithine decarboxylase (ODC) play a central role in the transmission of signals induced by growth factors. Therefore, we analyzed these gene products during the course of CIP and during the regeneration of the gland. Growth and biochemical parameters (pancreatic weight, total DNA, RNA and proteins) were determined along with ODC activity and quantitative reverse-transcriptase polymerase chain reaction measurements of mRNA levels. During CIP, the significant increases in pancreatic weight were the result of oedema. During that period, maximal increases in ODC activity were observed at 3 h, in ODC mRNA expression at 2, 3, and 4 h, and in Ki-ras mRNA expression at 1 h. During the 3-day resting period within which no treatment was given, pancreatic weight exhibited its maximal reduction after 2 days in the CIP group. In that same group, the ODC activity reached its maximal level above control after 3 days and ODC and Ki-ras mRNA expression after 1 and 2 days. During the regeneration period of 5 days, the pancreata of the untreated pancreatitis rats did not totally recover, whereas those of the animals receiving the small dose of caerulein (1 microgram) showed full recovery and even a significant increase above control after 5 days. During that period, maximal increases in ODC activity and Ki-ras mRNA expression occurred after 1 day of caerulein treatment; ODC mRNA expression was also significantly increased after 3 and 5 days in the pancreatitis animals with no effect of caerulein treatment. The positive effect of caerulein on Ki-ras mRNA suggests that the cholecystokinin analogue can induce the expression of essential growth-promoting genes.
...
PMID:Increases in Ki-ras and ornithine decarboxylase gene expression in rat pancreas after caerulein-induced pancreatitis. 891 8

Polyamines such as spermine or putrescine, resulting from increased activity of ornithine decarboxylase (ODC), are known for gastroprotective and mucosal growth promoting effects but little information is available about their role in the acceleration of the healing of stress-induced gastric lesions by epidermal growth factor (EGF). In this study, rats with intact or suppressed ODC activity by alpha-difluoromethylornithine (DFMO, 400 mg/kg i.p.) were subjected to 3.5 h of water immersion and restraint stress (WRS) without or with intragastric (i.g.) administration of spermine and putrescine or with subcutaneous (s.c.) injection of EGF. At 0, 2, 6, 12 and 24 h after stress, rats were killed and the number of gastric lesions was counted, gastric blood flow (GBF) was recorded by the H2-gas clearance technique, the gene expression of ODC mRNA using reverse-transcriptase polymerase chain reaction (RT-PCR) and the ODC activity in this mucosa were determined in oxyntic mucosa. Stress produced gastric lesions combined with decreased GBF (by approximately 43%), but at 2, 6, 12 and 24 h after stress, these lesions and the fall in GBF were gradually attenuated. Healing of stress lesions was accompanied by strong stimulation of ODC mRNA expression and by an immediate increase in enzyme activity, with a peak occurring about 6 h after stress. Pretreatment with DFMO or salivectomy (which resulted in a marked fall in luminal EGF levels and mucosal DNA synthesis) delayed significantly the healing of stress lesions. EGF or spermine significantly accelerated the ulcer healing and raised the GBF. Suppression of endogenous generation of prostaglandins (PGs) with indomethacin (5 mg/kg i.p.) almost completely reversed the EGF- and spermine-induced acceleration of the healing of stress lesions and the accompanying rise in GBF. DFMO significantly reduced the enhancement in healing and the rise in the GBF induced by EGF, but failed to influence those induced by exogenous spermine. The acceleration of the healing induced by spermine or EGF and accompanying hyperemia were not affected by salivectomy. We conclude that (1) upregulation of the ODC transcript, increased ODC activity and polyamines play an important role in mucosal recovery from stress lesions due to acceleration of mucosal repair and an increase in gastric microcirculation, (2) increased ODC activity and resulting excessive polyamine release appear to act as primary mediators of EGF-induced acceleration of healing of stress lesions and (3) endogenous PGs cooperate with EGF and polyamines in mucosal repair from stress ulcerations.
...
PMID:Involvement of ornithine decarboxylase and polyamines in epidermal growth factor-induced recovery of gastric mucosa from gastric lesions provoked by stress. 971 66

Mitogen-regulated protein/proliferin (mrp/plf) gene family transcripts rise in abundance as a response to diverse chemical and physical agents that promote morphological transformation in the murine C3H/10T1/2 cultured cell model of multi-step carcinogenesis. To determine if proliferin genes respond to tumor promoters in vivo, RNA was extracted from the whole skin of SENCAR mice after single applications of 2 or 20 microg 12-O-tetradecanoylphorbol-13-acetate (TPA); 3.2 or 32 nmole), 20 or 40 mg benzoyl peroxide (BPO; 83, 165 micromole), or acetone vehicle alone (2.72 mmole). RNA samples were prepared from treated skin areas, 2-48 h after painting. Mrp/plf-mRNA was not detected in Northern blot hybridizations, but large increases in mRNAs for ornithine decarboxylase gene and mRNA (odc), v-jun oncogene-related transcription factor gene and mRNA (junB), egr1 (early growth response protein gene and mRNA) were measured relative to beta 2 microglobulin gene and mRNA (b2m) mRNA in response to TPA. BPO induced small relative changes in these mRNAs. Reverse transcriptase (RT)-polymerase chain reactions (PCR) detected fully-processed MRP/plf-mRNA 16-48 h after TPA treatments in five of six animals, and in three of six BPO-treated animals. The MRP/plf-mRNA species expressed in the skin were predominantly plf1 and mrp3 as determined by gene-specific restriction enzyme sites within the RT-PCR products. Expression was either undetectable or found at low levels in acetone-painted controls and was not detected during the anagen phase of the normal hair growth cycle in unpainted animals. These results demonstrate that mrp/plf-mRNA is differentially expressed in murine skin in response to mechanistically distinct tumor promoters and has potential utility as a short-term biomarker for tumor promoting effects in chemical carcinogenesis.
...
PMID:Mitogen-regulated protein/proliferin mRNA induction following single applications of tumor promoters to murine skin. 1592 Jul 18

A four carbon linear chain diamine, putrescine (1,4-diaminobutane), is an important platform chemical having a wide range of applications in chemical industry. Biotechnological production of putrescine from renewable feedstock is a promising alternative to the chemical synthesis that originates from non-renewable petroleum. Here we report development of a metabolically engineered strain of Escherichia coli that produces putrescine at high titer in glucose mineral salts medium. First, a base strain was constructed by inactivating the putrescine degradation and utilization pathways, and deleting the ornithine carbamoyltransferase chain I gene argI to make more precursors available for putrescine synthesis. Next, ornithine decarboxylase, which converts ornithine to putrescine, was amplified by a combination of plasmid-based and chromosome-based overexpression of the coding genes under the strong tac or trc promoter. Furthermore, the ornithine biosynthetic genes (argC-E) were overexpressed from the trc promoter, which replaced the native promoter in the genome, to increase the ornithine pool. Finally, strain performance was further improved by the deletion of the stress responsive RNA polymerase sigma factor RpoS, a well-known global transcription regulator that controls the expression of ca. 10% of the E. coli genes. The final engineered E. coli strain was able to produce 1.68 g L(-1) of putrescine with a yield of 0.168 g g(-1) glucose. Furthermore, high cell density cultivation allowed production of 24.2 g L(-1) of putrescine with a productivity of 0.75 g L(-1) h(-1). The strategy reported here should be useful for the bio-based production of putrescine from renewable resources, and also for the development of strains capable of producing other diamines, which are important as nitrogen-containing platform chemicals.
...
PMID:Metabolic engineering of Escherichia coli for the production of putrescine: a four carbon diamine. 1971 72

High polyamine (PA) levels and ornithine decarboxylase (ODC) overexpression are well-known phenomena in many aggressive cancer types. We analyzed the expression of ODC and ODC-activity regulating genes antizymes 1-3 (OAZ1-3) and antizyme inhibitors 1-2 (AZ-IN1-2) in human neuroblastoma (NB) tumors and correlated these with genetic and clinical features of NB. Since ODC is a known target gene of MYCN, the correlation between ODC and MYCN was of special interest. Data were obtained from Affymetrix micro-array analysis of 88 NB tumor samples. In addition, mRNA expression levels of ODC, OAZ2 and MYCN in a MYCN-inducible NB cell line were determined by quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR). ODC mRNA expression in NB tumors was significantly predictive of decreased overall survival probability and correlated with several unfavorable clinical NB characteristics (all p < 0.005). Interestingly, high ODC mRNA expression also showed significant correlation with poor survival prognosis in Kaplan-Meier analyses stratified for patients without MYCN amplification, suggesting an additional role for ODC independent of MYCN. Conversely, high OAZ2 mRNA expression correlated with increased survival and with several favorable clinical NB characteristics (all p < 0.003). In addition, we provide first evidence of a role for MYCN-associated transcription factors MAD2 and MAD7 in ODC regulation. In NB cell cultures, ectopic overexpression of MYCN altered ODC but not OAZ2 mRNA levels. In conclusion, these data suggest that elevated ODC and low OAZ2 mRNA expression levels correlate with several unfavorable genetic and clinical features in NB, offering new insights into PA pathways and PA metabolism-targeting therapy in NB.
...
PMID:The polyamine metabolism genes ornithine decarboxylase and antizyme 2 predict aggressive behavior in neuroblastomas with and without MYCN amplification. 1996 Apr 35

Parasitism by the endoparasitoid wasp Pteromalus puparum causes alterations in the plasma proteins of Pieris rapae. Analysis of plasma proteins using a proteomic approach showed that seven proteins were differentially expressed in the host pupae after 24-h parasitism. They were masquerade-like serine proteinase homolog (MSPH), enolase (Eno), bilin-binding protein (BBP), imaginal disc growth factor (IDGF), ornithine decarboxylase (ODC), cellular retinoic acid binding protein (CRABP), and one unknown function protein. The full length cDNA sequences of MSPH, Eno, and BBP were successfully cloned using rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis indicated that the transcript levels of MSPH and BBP in the fat bodies of host pupae were inducible in response to the parasitism and their variations were consistent with translational changes of these genes after parasitism, while the transcript levels of Eno and IDGF were not affected by parasitism. This study will contribute to the better understanding of the molecular bases of parasitoid-induced host alterations associated with innate immune responses, detoxification, and energy metabolism.
...
PMID:Proteome changes in the plasma of Pieris rapae parasitized by the endoparasitoid wasp Pteromalus puparum. 2126 41


<< Previous 1 2 3 4

---