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

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Query: EC:2.7.7.48 (transcriptase)
9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholecystokinin (CCK) has been suggested to modulate insulin output. We have shown that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show little or no expression of the CCK-A receptor gene in the pancreas. We examined whether the CCK-A and CCK-B receptor genes are expressed in the islets and the role of CCK-A receptor in insulin secretion. Gene expressions of CCK receptors were determined by the reverse-transcriptase polymerase chain reaction (RT-PCR) followed by Southern blot hybridization and Northern transfer analysis using LETO rats as controls. Pancreatic endocrine function was examined in perfusion (exogenous CCK stimulation) and meal ingestion (endogenous CCK stimulation) studies. CCK-A receptor mRNA was detected in the islets of LETO rats but not OLETF rats. Expression of the CCK-B receptor gene was detected in both strains by RT-PCR. Insulin secretion was impaired in OLETF rats, but the insulin contents of OLETF and LETO rats were not different. No abnormalities were detected histologically in either strain. These results suggest that the occurrence of pancreatic endocrine dysfunction in OLETF rats may be due to a defect in expression of the CCK-A receptor gene, not to insulin deficiency.
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PMID:Pancreatic endocrine dysfunction in rats not expressing the cholecystokinin-A receptor. 883 Mar 28

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.
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PMID:Increases in Ki-ras and ornithine decarboxylase gene expression in rat pancreas after caerulein-induced pancreatitis. 891 8

The gastrointestinal peptides gastrin and cholecystokinin (CCK) stimulate growth of human pancreatic cancer through a CCK-B/gastrin- like receptor. In the present study we evaluated whether growth of human pancreatic cancer is endogenously regulated by gastrin. Immunohistomical examination of BxPC-3 cells and tumor xenografts revealed specifc gastrin immunoreactivity. Gastrin was detected by radioimmunoassay in pancreatic cancer cell extracts and in pancreatic cancer cell extracts and in the growth media. With use of reverse-transcriptase polymerase chain reaction gastrin gene expression was detected in both cultured BxPC-3 cancer cells and transplanted tumors, as well as seven addition human pancreatic cancer cell lines. Growth of BxPC-3 human pancreatic cancer cell in serum-free medium was inhibited by the addition of the CCK-B/gastrin receptor antagonist L-365,260, and gastrin treatment reversed the inhibitory effect of the antagonist. A selective gastrin antibody (Ab repressed growth of BxPC-3 cells. Gastrin immunoreactivity was detected in fresh human pancreatic cancer specimens but not in normal human pancreatic tissue. These data provide the first evidence that growth of a human pancreatic cancer is tonically stimulated by the autocrine production of gastrin. Evidence for the ubiquity of this system was provided by the detection of gastrin gene expression in multiple human pancreatic cancer cell lines and detection of gastrin in cell lines and fresh pancreatic tumors.
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PMID:Gastrin regulates growth of human pancreatic cancer in a tonic and autocrine fashion. 892 9

Phospholipase C (PLC) activity was investigated by stimulation of membrane preparations obtained from insulin (beta-TC3)-, somatostatin (Rin 1027-B2)-, and glucagon (INR1-G9)-producing pancreatic cell lines using the non-hydrolyzable GTP analogue GTPgammaS alone, the C-terminal octapeptide cholecystokinin (CCK-8), or gastrin. All compounds caused a significant 2- to 4.4-fold stimulation of PLC activity in the different cell lines, which was diminished by the non-hydrolyzable GDP analogue GDPbetaS. CCK receptor subtypes were characterized by radioligand binding experiments. High-affinity binding sites for tritiated CCK(A) receptor antagonist L-364,718 (K(d) = 0.24 nM) and tritiated CCK(B) receptor antagonist L-365,260 (K(d) = 0.13 nM) were only present in Rin 1027-B2 cells. High-affinity binding sites for both ligands were not found in beta-TC3 or INR1-G9 cells. Competition binding experiments with non-labeled CCK receptor antagonists CR 1505 (CCK(A) receptor-selective) and CR 2945 (CCK(B) receptor-selective), as well as microphysiometry experiments, resulted in the same receptor distribution. Reverse transcriptase-polymerase chain reaction confirmed the CCK receptor distribution pattern for Rin 1027-B2 cells, but in addition showed the existence of CCK(B) receptors in beta-TC3 cells. Immunoblocking experiments with C-terminal antibodies against different G-protein alpha-subunits demonstrated inhibition of CCK-stimulated PLC activity in beta-TC3 cells by G(q/11)alpha antiserum (70%), in Rin 1027-B2 cells by G(q/11)alpha antiserum (70%) and G(i)-3alpha antiserum (23%), and in INR1-G9 cells by G(q/11)alpha antiserum (60%) and G(o)alpha antiserum (45%). We conclude that CCK receptor subtypes with different G-protein-coupling specificities to PLC are present in the different hormone-secreting cells of the endocrine pancreas.
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PMID:Activation of phospholipase C by cholecystokinin receptor subtypes with different G-protein-coupling specificities in hormone-secreting pancreatic cell lines. 1093 May 42

Leptin was shown to exhibit similar to cholecystokinin (CCK) cytoprotective activity against acute gastric lesions, but its role in ulcer healing has not been examined. The aims of this study were: (1) to compare the effects of exogenous leptin to those of CCK on the course of healing of chronic gastric ulcers; (2) to study the gene and protein expression of leptin at the ulcer margin during ulcer healing; and (3) to assess the effects of leptin administration on the mucosal gene expression of main growth factor such as transforming growth factor alpha (TGFalpha). Gastric ulcers were produced in rats by the acetic acid method. Rats with ulcers were divided in following treatment groups: (1) vehicle; (2) leptin (10 microg/kg i.p.); (3) CCK (10 microg/kg s.c.); and (4) leptin or CCK with or without tyrphostin A46 (200 microg/kg i.p.), an inhibitor of epidermal growth factor (EGF)-receptor tyrosine kinase or NG-nitro-L-arginine (20 mg/kg i.g.), a blocker of nitric oxide synthase. Animals were euthanized 9 days after ulcer induction. The area of gastric ulcers and the gastric blood flow at the ulcer area were determined. In addition, mucosal biopsy samples were taken from the ulcer area for histological evaluation as well as for the determination of mRNA and protein expression for leptin and constitutive nitric oxide synthase (cNOS) and inducibile nitric oxide synthase (iNOS) by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot, respectively. In addition, the gene expression for TGFalpha was analyzed by RT-PCR. Both leptin and CCK reduced significantly the ulcer area as compared to vehicle-treated group by approximately 50%. The treatment with tyrphostin or N(G)-nitro-L-arginine reversed in part the acceleration of ulcer healing by leptin and CCK. The expression of leptin mRNA and protein was significantly increased at the ulcer edge. The leptin-induced acceleration of ulcer healing was associated with increased expression of transcripts for TGFalpha as well as increased mRNA and protein expression for cNOS and iNOS at the ulcer margin. We conclude that leptin accelerates ulcer healing by mechanisms involving the up-regulation of TGFalpha and increased production of nitric oxide due to up-regulation of cNOS and iNOS in the ulcer area.
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PMID:Role of leptin in ulcer healing. 1123 Sep 99

The prevalence of esophageal adenocarcinoma in the setting of Barrett's metaplasia continues to increase in Western nations at a rate greater than any other cancer. The trophic properties of gastrin have been documented in gastric, pancreatic and colon cancer cell lines, suggesting a potential role for this regulatory peptide in the growth of these malignancies. The aims of these studies were to identify and characterize the presence of functional cholecystokinin type-2 (gastrin) receptors on the membranes of human esophageal adenocarcinoma cells. Reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated the presence of cholecystokinin type-2 receptor transcripts in human esophageal adenocarcinoma cell lines. Competitive binding assays revealed specific binding of gastrin in SEG-1 cells (IC50 of 2.4 x 10(-8) M). This finding was confirmed by laser scanning confocal microscopy through internalization of rhodamine green labeled gastrin heptapeptide in SEG-1 cells. Gastrin caused a dose-dependent increase in proliferation of SEG-1 cells when compared to controls. This effect was abolished by co-incubation with L365,260, a CCK-2-specific receptor antagonist. Gastrin-induced phosphorylation of the p44 and p42 mitogen-activated protein kinases was demonstrated by Western blot analysis. In conclusion, the studied human esophageal adenocarcinoma cell lines possess cholecystokinin type-2 (gastrin) receptors. Receptors bind gastrin, resulting in increased proliferation in SEG-1 cells.
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PMID:Gastrin stimulates receptor-mediated proliferation of human esophageal adenocarcinoma cells. 1517 38

The toxicity of pulp and paper mill effluents (PPMEs) has been greatly decreased, yet some continue to negatively affect fish reproduction. We hypothesized that PPMEs are affecting the brain resulting in decreased reproductive performance. Our goal was to use gene expression profiling to test the hypothesis that PPMEs are having an effect on neural systems in the fathead minnow (FHM; Pimephales promelas) in vivo. Sexually mature male and female FHM were exposed to 100% final biotreated PPMEs from 5 different sources for 5 days. Using an oligo-array (15K genes) we examined the effect of PPMEs on gene expression in the hypothalamus of female fish. We validated selected genes (cholecystokinin, RevErbbeta2, and urotensin I) that were identified by microarray analysis using real-time reverse-transcriptase polymerase chain reaction (RT-PCR). We compared the FHM microarray dataset to multiple microarray datasets from experiments conducted with goldfish injected with different dopaminergic pharmaceuticals to examine whether PPMEs could be affecting the dopamine system. Exposure of FHM to PPMEs resulted in varying degrees of spawning inhibition. Microarray analysis revealed surprisingly few genes in the brain that were commonly affected by the different PPMEs. Real-time RT-PCR confirmed the changes in expression for cholecystokinin, RevErbbeta2, and urotensin I. Comparison of the FHM and goldfish microarray datasets suggest that some PPMEs may be acting on the dopamine system. We show that PPMEs are neuroactive in fish and may be acting through some of the pathways in a manner similar to dopamine.
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PMID:Gene expression profiling of the fathead minnow (Pimephales promelas) neuroendocrine brain in response to pulp and paper mill effluents. 2056 91

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