Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Helicobacter pylori strains isolated from most patients with peptic ulcer disease and adenocarcinoma express the vacuolating toxin VacA and contain a pathogenicity island named cag. The cag pathogenicity island codes for more than 40 putative proteins with features similar to bacterial secretion systems. One of these proteins, CagA, is an immunodominant antigen with unknown function encoded by the cagA gene. In the present study, we have analysed the functional promoter elements of the H. pylori cagA gene as well as of the divergently transcribed cagB gene. Primer extension analyses identified a single 5' end of the cagA mRNA, while two initiation sites were mapped in the case of the cagB mRNA. The promoters deduced upstream of these start points of transcription contained conserved -10 regions but no -35 regions with respect to the Escherichia coli sigma70 consensus sequence. Nevertheless, they could be activated in E. coli and in vitro by purified E. coli RNA polymerase. Deletion analyses indicated that the cagA and cagB genes are transcribed by overlapping promoters and that full activation requires sequences up to -70 and -96 respectively. Instead, basal transcription is likely to be mediated by -10 extended promoter-like sequences. RNA polymerase is able to bind the -40 to -60 region of the cagA promoter, and its binding is mediated by the alpha-subunit. This region resembles the UP elements of prokaryotic promoters in location, sequence and mechanism of interaction with the RNA polymerase. We discuss the features of these promoters and propose that they could represent a class of minimum promoters, which ensures a basic level of transcription, while full activation requires regulatory elements or a defined promoter context.
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PMID:Transcriptional analysis of the divergent cagAB genes encoded by the pathogenicity island of Helicobacter pylori. 938 60

The antiulcer effect of bisdemethoxycurcumin, a yellow pigment found mainly in rhizomes of Curcuma longa, was compared with curcumin in gastric ulcer model systems to validate its clinical application as a remedy for peptic ulcer. Western blot analysis of mouse macrophage cell line RAW 264.7 activated with lipopolysaccharide showed that bisdemethoxycurcumin inhibited inducible nitric oxide synthase (iNOS) production significantly but had no effect on tumor necrosis factor-alpha (TNF-alpha) production, whereas curcumin showed stronger suppression of iNOS protein production and inhibited TNF-alpha protein production significantly. However, bisdemethoxycurcumin and curcumin possessed similar potency in scavenging nitric oxide generated from mouse macrophage cell line RAW 264.7. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis showed that both curcuminoids inhibited the induction of iNOS dose-dependently at the transcriptional level and curcumin also appeared to inhibit the induction of TNF-alpha at post-transcriptional level. In an animal model, intraduodenal administration of bisdemethoxycurcumin (5-80 mg/kg body wt.) showed a strong inhibitory effect on gastric acid secretion in pylorus-ligated rats whereas curcumin (5-20 mg/kg body wt.) showed a less inhibitory effect, with maximum potency at a dose of 20mg/kg body wt. Moreover, oral administration of bisdemethoxycurcumin at doses of 20-80 mg/kg body wt. twice daily for 10 days showed a significant curative efficacy in accelerating the healing of acetic acid-induced chronic gastric ulcer and promotion of mucosal regeneration in the ulcerated portion in a dose-related manner with potency equal to curcumin. In contrast, the curative potency of curcumin tended to decrease at doses over 160 mg/kg body wt./day. Western blot analysis in ulcerated gastric mucosa showed that bisdemethoxycurcumin dose-dependently reduced the increased protein expression level of iNOS but not TNF-alpha. These results indicated that bisdemethoxycurcumin directly accelerates gastric ulcer healing with potency equal to curcumin. Its antiulcer effect might be due to its properties of decreasing gastric acid secretion and enhancing the mucosal defensive mechanism through suppression of iNOS-mediated inflammation.
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PMID:Comparative antiulcer effect of bisdemethoxycurcumin and curcumin in a gastric ulcer model system. 1918 55

Rifamycins inhibit RNA polymerase of most bacterial genera. Rifampicin remains part of combination therapy for treating tuberculosis (TB), and for treating Gram-positive prosthetic joint and valve infections, in which biofilms are prominent. Rifabutin has use for AIDS patients in treating mycobacterial infections TB and Mycobacterium avium complex (MAC), having fewer drug-drug interactions that interfere with AIDS medications. Rifabutin is occasionally used in combination to eradicate Helicobacter pylori (peptic ulcer disease). Rifapentine has yet to fulfill its potential in reducing time of treatment for TB. Rifaximin is a monotherapeutic agent to treat gastrointestinal (GI) disorders, such as hepatic encephalopathy, irritable bowel syndrome, and travelers' diarrhea. Rifaximin is confined to the GI tract because it is not systemically absorbed on oral dosing, achieving high local concentrations, and showing anti-inflammatory properties in addition to its antibacterial activity. Resistance issues are unavoidable with all the rifamycins when the bioburden is high, because of mutations that modify RNA polymerase.
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PMID:Rifamycins, Alone and in Combination. 2727 May 59