PubMed Health⌕ Search

Biomedical subjects

Supratim Choudhuri

Publications and source records attributed to Supratim Choudhuri.

8 recordsLinked to original sources
PubMed2005

Usefulness of studies on the molecular mechanism of action of herbals/botanicals: The case of St. John's wort.

The use of herbals/botanicals has been gaining wide popularity in recent years in the United States as well as in other parts of the world. The mechanism of action of most of these herbals/botanicals has not been subjected to thorough scientific investigations. St. John's wort (Hypericum perforatum) represents a useful case study in this sense. Traditionally, it is used as a natural treatment for depression; however, in recent years its molecular mechanism of action has been elucidated by a number of laboratories across the world. Such studies have helped understand potential interactions of St. John's wort with drugs and other xenobiotics. St. John's wort activates a nuclear receptor called pregnane X receptor (PXR). PXR is a ligand-activated transcription factor that induces a number of xenobiotic-metabolizing enzymes and transporters including cytochrome P4503A4 (CYP3A4) in humans. Because CYP3A4 alone metabolizes about 60% of all clinically relevant drugs, induction of CYP3A4 may result in the rapid elimination of these drugs and a consequent reduction in drug efficacy. Ironically, such enzyme-inducing effects may not produce any immediate adverse symptomatology in the person taking St. John's wort. Therefore, the case of St. John's wort should serve as a good example of the usefulness and importance of studies on the mechanism of action of the herbals/botanicals, particularly those with widespread use. Scientists, physicians, and other health professionals can make use of the knowledge from such studies as an additional risk management tool.

Animals↗
PubMed2004

Microarrays in biology and medicine.

The remarkable speed with which biotechnology has become critical to the practice of life sciences owes much to a series of technological revolutions. Microarray is the latest invention in this ongoing technological revolution. This technology holds the promise to revolutionize the future of biology and medicine unlike any other technology that preceded it. Development of microarray technology has significantly changed the way questions about diseases and/or biological phenomena are addressed. This is because microarrays facilitate monitoring the expression of thousands of genes or proteins in a single experiment. This enormous power of microarrays has enabled scientists to monitor thousands of genes and their products in a given living organism in one experiment, and to understand how these genes function in an orchestrated manner. Obtaining such a global view of life at the molecular level was impossible using conventional molecular biological techniques. However, despite all the progress made in developing this technology, microarray is yet to reach a point where all data are obtained, analyzed, and shared in a standardized fashion. The present article is a brief overview of microarray technologies and their applications with an emphasis on DNA microarray.

Animals↗
PubMed2004

Structural analysis of CYP2C9 and CYP2C5 and an evaluation of commonly used molecular modeling techniques.

This work had two separate aims: to evaluate different modeling techniques and to make a detailed structural characterization of CYP2C9. To achieve these goals, the consensus principal component analysis (CPCA) technique and distance measurements were used to explore available crystal structures, newly built homology models, and repeated molecular dynamics simulations. The CPCA was based on molecular interaction fields focused on the active site regions of the proteins and include detailed amino acid analysis. The comparison of the CYP2C9 and CYP2C5 crystal structures revealed differences in the flexible regions such as the B-C and F-G loop and the N and C termini. Cross homology models of CYP2C9 and CYP2C5, using their respective crystal structures as templates, indicated that such models were more similar to their templates than to their target proteins. Inclusion of multiple templates slightly improved the similarity to the crystal target in some cases and could be recommended even though it requires a careful manual alignment process. The application of molecular dynamics simulations to highly flexible proteins such as cytochromes P450 is also explored and the information is extracted by the CPCA. Advantages and drawbacks are presented for the different modeling techniques. Despite the varying modeling success, the models give insight and understanding by the mutual forming and discarding of hypotheses. This is a dynamic process since the crystal structures are improving with time and, therefore, the answers to the models are also changing accordingly.

Aryl Hydrocarbon Hydroxylases↗
PubMed2003

Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of rats.

The aim of this study was to quantitatively determine the constitutive expression levels of various transporter mRNAs in rat choroid plexus. To provide a reference for the relative expression levels, the expression of various transporter mRNAs in choroid plexus were compared with that in liver, kidney, and ileum. The mRNA levels of multidrug resistance protein (Mrp)1, 2, 3, 4, 5, and 6; multidrug resistance (Mdr)1a, 1b, and 2; organic anion transporting polypeptide (Oatp)1, 2, 3, 4, 5, 9, 12, and Oat-K (1/2); organic anion transporter (Oat)1, 2, and 3; organic cation transporter (Oct)1, 2, 3, N1, and N2; bile acid transporters sodium taurocholate cotransporting polypeptide (Ntcp), bile salt excretory protein (Bsep), and ileal bile acid transporter (Ibat); divalent metal transporter 1 (DMT1), Menke's and Wilson's metal transporters; equilibrative nucleotide transporters (Ent) 1 and 2, and constitutive nucleotide transporters (Cnt)1 and 2; peptide transporters (Pept)1 and 2; as well as ATP-binding cassette (Abc)G5 and 8 were measured in choroid plexus by the branched DNA signal amplification method. Mrp1, 4, and 5, Oatp3, Menke's transporter, DMT1, Ent1, and Pept2 mRNAs were expressed in choroid plexus at higher levels than in liver, kidney, or ileum. OctN1 and N2, Oatp2, Oat2 and 3, and Cnt1 and 2 mRNAs expressions were detectable in choroid plexus, but the levels were lower compared with that in liver, kidney, or ileum. The remaining transporters [Mrp2, Mrp3, Oct1, Oct2, Oatp1, Oatp4, Oatp5, Oatp12, Oat-K (1/2), Ntcp, Bsep, Ibat, Mdr1a, Mdr1b, Mdr2, Oat1, Ent2, Pept1, AbcG5, AbcG8] were expressed at very low levels in choroid plexus. The constitutive expression levels of different transporters in choroid plexus may provide an insight into the range of xenobiotics that can potentially be transported by the choroid plexus, thereby providing a means of xenobiotic detoxification in the brain.

Animals↗
PubMed2002

Induction profile of rat organic anion transporting polypeptide 2 (oatp2) by prototypical drug-metabolizing enzyme inducers that activate gene expression through ligand-activated transcription factor pathways.

Knowledge of regulation of transporters would aid in predicting pharmacokinetics and drug-drug interactions. Treatment of rats with pregnenolone-16alpha-carbonitrile (PCN) and phenobarbital increases hepatic uptake of cardiac glycosides. Rat organic anion transporting polypeptide 2 (oatp2; Slc21a5) transports cardiac glycosides with high affinity. Levels of rat hepatic oatp2 protein and mRNA are regulated by PCN and phenobarbital treatment; however, the effects of other microsomal enzyme inducers on oatp2 have not been investigated. Therefore, the purpose of this study was to further determine whether oatp2 is regulated by a broader scale of drug-metabolizing enzyme inducers that are ligands or activators for the aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor (PPAR), and antioxidant/electrophile response element (ARE/EpRE). Oatp2 protein levels determined by Western blot were decreased 56 to 72% by the AhR ligands, increased 84 to 132% by the CAR ligands, and increased 230 to 360% by PXR ligands. The PPAR ligands and ARE/EpRE activators generally had minimal effects on oatp2 protein levels. Oatp2 mRNA levels, determined by the bDNA technique, generally did not show a correlation with the altered oatp2 protein levels, e.g., among PXR ligands, only PCN increased oatp2 mRNA levels, but spironolactone and dexamethasone did not. Furthermore, only PCN, but not spironolactone and dexamethasone, increased the transcription of the oatp2 gene as the amount of hnRNA was increased when determined by reverse transcription-polymerase chain reaction. In conclusion, some drug-metabolizing enzyme inducers regulate oatp2 protein levels, especially the CYP3A inducers. However, there is no correlation between their ability to increase levels of oatp2 protein and mRNA, suggesting that regulation of oatp2 by drug-metabolizing enzyme inducers occurs at both the transcriptional and post-translational levels.

Animals↗
PubMed2002

Gender-specific and developmental influences on the expression of rat organic anion transporters.

Rat organic anion transporter 1 (Oat1), Oat2, and Oat3, members of the organic anion transporter family, transport some organic anions across cellular membranes. Previously, highest Oat1 and Oat3 mRNA expression was reported in kidney and Oat2 in liver. However, gender and developmental differences in Oat expression remain unknown. This study describes gender- and age-specific patterns of rat organic anion transporter expression in various tissues. Oat mRNA expression was evaluated in adult male and female Sprague-Dawley rat tissues, and developmental expression was also determined in kidneys of Sprague-Dawley rats ranging in age from days 0 through 45. Expression was quantified using branched-DNA signal amplification. Oat1 mRNA expression was primarily observed in kidney. Surprisingly, Oat2 mRNA expression was also highest in kidney rather than in liver. Moreover, considerably higher Oat2 levels were seen in female kidney as compared with male. Finally, Oat3 mRNA expression was highest in kidney of both genders, whereas a male-predominant pattern was observed in liver. At birth, all kidney Oat mRNA levels were low. Renal Oat1 expression gradually increased throughout development, approaching adult levels at 30 days of age, where at days 40 and 45 Oat1 levels were greater in males than females. Oat2 expression in kidney was minimal through day 30 but increased dramatically at day 35 in females only. Lastly, Oat3 mRNA expression in kidney matured earliest, rapidly increasing from birth through day 10. These data indicate that Oat mRNA expression is primarily localized to the kidney, and observed expression patterns may explain some previously recognized age- and gender-dependent toxicities associated with chemical exposure.

Aging↗
PubMedDate not supplied

Structure, function, expression, genomic organization, and single nucleotide polymorphisms of human ABCB1 (MDR1), ABCC (MRP), and ABCG2 (BCRP) efflux transporters.

The ATP-binding cassette (ABC) transporters constitute a large family of membrane proteins, which transport a variety of compounds through the membrane against a concentration gradient at the cost of ATP hydrolysis. Substrates of the ABC transporters include lipids, bile acids, xenobiotics, and peptides for antigen presentation. As they transport exogenous and endogenous compounds, they reduce the body load of potentially harmful substances. One by-product of such protective function is that they also eliminate various useful drugs from the body, causing drug resistance. This review is a brief summary of the structure, function, and expression of the important drug resistance-conferring members belonging to three subfamilies of the human ABC family; these are ABCB1 (MDR1/P-glycoprotein of subfamily ABCB), subfamily ABCC (MRPs), and ABCG2 (BCRP of subfamily ABCG), which are expressed in various organs. In the text, the transporter symbol that carries the subfamily name (such as ABCB1, ABCC1, etc.) is used interchangeably with the corresponding original names, such as MDR1P-glycoprotein, MRP1, etc., respectively. Both nomenclatures are maintained in the text because both are still used in the transporter literature. This helps readers relate various names that they encounter in the literature. It now appears that P-glycoprotein, MRP1, MRP2, and BCRP can explain the phenomenon of multidrug resistance in all cell lines analyzed thus far. Also discussed are the gene structure, regulation of expression, and various polymorphisms in these genes. Because genetic polymorphism is thought to underlie interindividual differences, including their response to drugs and other xenobiotics, the importance of polymorphism in these genes is also discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗