Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Mycobacterium tuberculosis strains of genotype A1 (LAM family, VNTR profile 222222) are often resulted from people with pulmonary tuberculosis, who live in Central Russia. Among strains of this family, drug-resistant strains, including those with simultaneous resistance to isoniazid and rifampicin (MDR), are common. The strains of the genotype A1 tend to spread as clones.
Mol Gen Mikrobiol Virusol 2006
PMID:[Characteristics of Mycobacterium tuberculosis clinical strains genotype A1]. 1675

Anti-tuberculosis drugs are a two-edged sword. While they destroy pathogenic M. tuberculosis they also select for drug resistant bacteria against which those drugs are then ineffective. Global surveillance has shown that drug resistant Tuberculosis is widespread and is now a threat to tuberculosis control programs in many countries. Application of molecular methods during the last decade has greatly changed our understanding of drug resistance in tuberculosis. Application of molecular epidemiological methods was also central to the description of outbreaks of drug resistance in Tuberculosis. This review describes recommendations for Tuberculosis treatment according to the WHO guidelines, the drug resistance problem in the world, mechanisms of resistance to first line and second line drugs and applications of molecular methods to detect resistance causing gene mutations. It is envisaged that molecular techniques may be important adjuncts to traditional culture based procedures to rapidly screen for drug resistance. Prospective analysis and intervention to prevent transmission may be particularly helpful in areas with ongoing transmission of drug resistant strains as recent mathematical modeling indicate that the burden of MDR-TB cannot be contained in the absence of specific efforts to limit transmission.
Curr Issues Mol Biol 2006 Jul
PMID:Drug resistance in Mycobacterium tuberculosis. 1687 62

Determining the functional aspects of a gene or protein is a difficult and time-consuming process. De novo analysis is surely the hardest and so it is often quite useful to start with a comparison to functionally or structurally related proteins. Although 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD 1) can hardly be called a new protein but rather the best characterized among the family of 17beta-HSDs some aspects of structure-function relationships remain unclear. We have sought new aspects of 17beta-HSD 1 function through a comparison with its closest homolog, a photoreceptor-associated retinol dehydrogenase (prRDH). Overall amino acid identity and size of the proteins are highly conserved, but major differences occur in the C-termini, where prRDH, but not 17beta-HSD 1, harbors motifs indicative of membrane localization. To gain insight into substrate discrimination by prRDH and 17beta-HSD 1, we constructed 3D-structure models of the corresponding zebrafish enzymes. Investigation of the substrate binding site revealed a few identical amino acids, and suggested a role for G143 in zebrafish 17beta-HSD 1 and M146 and M147 in the two zebrafish paralogs prRDH 1 and prRDH 2, respectively, in substrate specificity. Activity measurements of modified proteins in transiently transfected intact HEK 293 cells hint at a putative role of these amino acids in discrimination between steroid and retinoid substrates.
J Steroid Biochem Mol Biol 2007 May
PMID:Functional aspects of 17beta-hydroxysteroid dehydrogenase 1 determined by comparison to a closely related retinol dehydrogenase. 1746 81

Three retinol dehydrogenases (RDHs) were tested for steroid converting abilities: human and murine RDH 12 and human RDH13. RDH12 is involved in retinal degeneration in Leber's congenital amaurosis (LCA). We show that murine Rdh12 and human RDH13 do not reveal activity towards the checked steroids, but that human type 12 RDH reduces dihydrotestosterone to androstanediol, and is thus also involved in steroid metabolism. Furthermore, we analyzed both expression and subcellular localization of these enzymes.
J Steroid Biochem Mol Biol 2007 May
PMID:RDH12, a retinol dehydrogenase causing Leber's congenital amaurosis, is also involved in steroid metabolism. 1751 23

Fibroids are benign neoplasms of myometrial smooth muscle cells (SMC). Despite being the most common tumor in humans, their etiology is poorly understood. Recent microarray studies have demonstrated that multiple members of the retinoid pathway are differentially expressed between myometrium and fibroids. The aim of this present study was to investigate gene expression of members of the retinoid pathway in matched myometrium and fibroids. We have demonstrated differential gene expression of two binding proteins [cellular retinol-binding proteins (CRBP) 1 and 2], three enzymes [alcohol dehydrogenase 1 (ADH1), aldehyde dehydrogenase (ALDH1) and retinol dehydrogenase (RODH)] and two receptors [retinoid X receptors (RXR) alpha and gamma] involved in the retinoid pathway by real-time PCR. There were no differences in gene expression for retinoid receptors RARalpha, beta, gamma and RXRbeta, and for the metabolizing enzyme cytochrome P450, family 26 subfamily A. We confirmed results for ADH1, ALDH1, CRBP1 and CRABP2 at the protein level by western blot. Using immunohistochemistry these proteins were mostly localized to myometrial and fibroid SMC. An exception to this was ALDH1 protein, which displayed strong staining localized to cells of the connective tissue, presumably fibroblasts, with a striking differential expression pattern between myometrium and fibroids. These results demonstrate that the retinoid pathway is altered in fibroids when compared with normal myometrium and specifically identify ALDH1 in fibroid fibroblasts. These alterations can lead to aberrant retinoic acid (RA) production and signaling, and alter the expression of RA target genes, which may be an important step in fibroid development.
Mol Hum Reprod 2007 Aug
PMID:Retinoic acid pathway genes show significantly altered expression in uterine fibroids when compared with normal myometrium. 1755 14

The multidrug resistance gene 1 (MDR1) product, P-glycoprotein (P-gp), pumps out a variety of anticancer agents from the cell, including anthracyclines, Vinca alkaloids, and taxanes. The expression of P-gp therefore confers resistance to these anticancer agents. In our present study, we found that FTI-277 (a farnesyltransferase inhibitor), U0126 [an inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)], and 17-allylamino-17-demethoxygeldanamycin (an inhibitor of heat shock protein 90) reduced the endogenous expression levels of P-gp in the human colorectal cancer cells, HCT-15 and SW620-14. In contrast, inhibitors of phosphatidylinositol 3-OH kinase, mammalian target of rapamycin, p38 mitogen-activated protein kinase, and c-Jun NH(2)-terminal kinase did not affect P-gp expression in these cells. We further found that U0126 down-regulated exogenous P-gp expression in the MDR1-transduced human breast cancer cells, MCF-7/MDR and MDA-MB-231/MDR. However, the MDR1 mRNA levels in these cells were unaffected by this treatment. PD98059 (a MEK inhibitor), ERK small interfering RNA, and p90 ribosomal S6 kinase (RSK) small interfering RNA also suppressed P-gp expression. Conversely, epidermal growth factor and basic fibroblast growth factor enhanced P-gp expression, but the MDR1 mRNA levels were unchanged in epidermal growth factor-stimulated cells. Pulse-chase analysis revealed that U0126 promoted P-gp degradation but did not affect the biosynthesis of this gene product. The pretreatment of cells with U0126 enhanced the paclitaxel-induced cleavage of poly(ADP-ribose) polymerase and paclitaxel sensitivity. Furthermore, U0126-treated cells showed high levels of rhodamine123 uptake. Hence, our present data show that inhibition of the MEK-ERK-RSK pathway down-regulates P-gp expression levels and diminishes the cellular multidrug resistance.
Mol Cancer Ther 2007 Jul
PMID:Inhibition of the mitogen-activated protein kinase pathway results in the down-regulation of P-glycoprotein. 1762 Apr 38

Membrane proteins responsible for the active efflux of structurally and functionally unrelated drugs were first characterized in higher eukaryotes. To date, a vast number of transporters contributing to multidrug resistance (MDR transporters) have been reported for a large variety of organisms. Predictions about the functions of genes in the growing number of sequenced genomes indicate that MDR transporters are ubiquitous in nature. The majority of described MDR transporters in bacteria use ion motive force, while only a few systems have been shown to rely on ATP hydrolysis. However, recent reports on MDR proteins from gram-positive organisms, as well as genome analysis, indicate that the role of ABC-type MDR transporters in bacterial drug resistance might be underestimated. Detailed structural and mechanistic analyses of these proteins can help to understand their molecular mode of action and may eventually lead to the development of new strategies to counteract their actions, thereby increasing the effectiveness of drug-based therapies. This review focuses on recent advances in the analysis of ABC-type MDR transporters in bacteria.
Microbiol Mol Biol Rev 2007 Sep
PMID:Distribution and physiology of ABC-type transporters contributing to multidrug resistance in bacteria. 1780 67

Recently in Russia biochips for rifampin resistance detection of M. tuberculosis were developed. To investigate the conformity between rifampin resistance results determined both by the routinely used absolute concentration method and USING the biochips, 272 DNA samples of M. tuberculosis isolated from TB patients at Novosibirsk and Tomsk regions in 2000-2005 were analyzed. The biochip can detect 30 mutations in rpoB gene. The mutations were also tested using the single stranded conformational polymorphism method (SSCP). In addition, 60 DNAs were randomly sampled and sequenced. The results of rifampin resistance detection using biochip and absolute concentration methods were congruent in 86% cases, and were different when analyzed samples consisted of the susceptible and resistant strains of M. tuberculosis mixture. The most frequent mutations in the rpoB gene were S531 (76.2%), H526 (7%), D516 (5.6%), and L511 (5.6%). In 94% of rifampin resistant strains, there was also resistance to isoniazid. Therefore, in Siberia the rifampin resistance is the reliable marker for MDR strains of M. tuberculosis, and biochips can be used also for their detection. To hybridize with biochip the fluorescent-labeled single-stranded DNAs were routinely synthesized by two PCR, and intermediary product after the first PCR should be transferred into another tube. The last stage included high risk of cross-contamination. To exclude the risk, primer concentrations and temperature-time profile of PCR reactions were improved, and both PCR were combined in one tube. The two methods were congruent in 100%. The one tube method would be especially attractive for the routine PCR laboratory.
Mol Gen Mikrobiol Virusol 2007
PMID:[Evaluation of biochips for the rifampin resistance detection of M. tuberculosis in strains isolated at the Novosibirsk and Tomsk regions]. 1788 68

Overexpression of the multidrug resistance 1 (MDR1) gene, encoding P-glycoprotein (P-gp), facilitates resistance to diverse chemotherapeutic drugs and current P-gp inhibitors display high toxicity. We studied the effects of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), which exhibits cancer-specific apoptosis-inducing properties, in drug-sensitive (SW620) and drug-resistant (SW620/Dox) colorectal carcinoma cells. Adenovirus administered mda-7/IL-24, Ad.mda-7, effectively reversed resistance to doxorubicin-induced apoptosis in SW620/Dox cells by increased intracellular accumulation and decreased efflux of doxorubicin. Unexpectedly, P-gp-overexpressing cells (SW620/Dox) displayed increased apoptosis following Ad.mda-7 infection compared with parental SW620 cells, which correlated with more MDA-7/IL-24 protein in SW620/Dox than SW620 cell and potentially explains the increased sensitivity of P-gp-overexpressing cells to mda-7/IL-24. Transient overexpression of MDR1 in SW620 cells significantly increased apoptosis, decreased anchorage-independent growth, and increased MDA-7/IL-24 protein following Ad.mda-7 infection, whereas down-modulation of MDR1 in SW620/Dox cells by small interfering RNA decreased apoptosis following Ad.mda-7 infection. The increased mda-7/IL-24 sensitivity observed in SW620/Dox cells was partly due to increased reactive oxygen species generation and lower mitochondrial membrane potential. These findings confirm that mda-7/IL-24 is a potent MDR reversal agent, preferentially causing apoptosis in P-gp-overexpressing MDR cells, suggesting significant expanded clinical implications for the use of mda-7/IL-24 in treating neoplasms that have failed chemotherapy mediated by the P-gp MDR mechanism.
Mol Cancer Ther 2007 Nov
PMID:Melanoma differentiation associated gene-7/interleukin-24 reverses multidrug resistance in human colorectal cancer cells. 1802 83

An immunological subtraction approach, surface-epitope masking (SEM), is described that permits the efficient and selective production of monoclonal antibodies (MAbs) reacting with both known and unknown molecules expressed on the cell surface. The tenet underlying SEM involves blocking (masking) of shared antigens between two target populations, a "driver" and a "tester," and using appropriately modified surface-masked "tester" cells to generate MAbs reacting with surface antigens unique to the "tester population" that differentiate the two antigen sources. SEM has been employed to develop MAbs that react with the multidrug resistance surface-expressed P-glycoprotein (MDR-1) and the human interferon-gamma receptor and two potentially novel tumor-associated antigens (TAAs) expressed on the surface of prostate carcinoma and breast carcinoma cells. In principle, the SEM approach provides an uncomplicated and effective means of developing MAbs, which can also be used to identify genes, associated with important cellular processes involved in normal physiology, such as growth, aging, differentiation, and development. In addition, this strategy is amenable to produce MAbs and identify genes associated with specific disease states, including cancer, neurodegeneration, autoimmunity, and infection with pathogenic agents.
Methods Mol Biol 2007
PMID:Surface-epitope masking (SEM): an immunological subtraction approach for developing monoclonal antibodies targeting surface-expressed molecules. 1821 90


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