We have investigated the spatial relationship between sites containing newly synthesized RNA and domains containing proteins involved in transcription, such as RNA polymerase II and the transcription factors TFIIH, Oct1, BRG1, E2F-1 and glucocorticoid receptors, using dual immunofluorescence labelling followed by confocal microscopy on cultured cells. As expected, a high degree of colocalisatio...

Nitric oxide, generated by the inducible form of nitric oxide synthase (iNOS), is a potential mediator of cytokine-induced beta-cell dysfunction in type 1 diabetes mellitus. We have previously shown that cytokine-induced iNOS expression is cycloheximide (CHX) sensitive and requires nuclear factor-kappa B (NF-kappa B) activation. In the present study, we show that an octamer motif located 20 bp ...

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 a...

The Serum and Glucocorticoid-regulated Kinase1 (SGK1) gene is a target of the glucocorticoid receptor (GR) and is central to the stress response in many human tissues. Because environmental stress varies across habitats, we hypothesized that natural selection shaped the geographic distribution of genetic variants regulating the level of SGK1 expression following GR activation. By combining popu...

In airway epithelia, non-neuronal cholinergic regulations have been described; however, the route for acetylcholine (ACh) release has not been verified. To investigate whether organic cation transporters (OCTs) serve this function, we studied the expression of OCTs in airway epithelia and their capability to translocate ACh. Using immunohistochemistry in rats and humans, OCT1, OCT2, and OCT3 we...

This article summarizes 4 phase 1 trials that explored interactions between the novel, triazole antifungal isavuconazole and substrates of the drug transporters breast cancer resistance protein (BCRP), multidrug and toxin extrusion protein-1 (MATE1), organic anion transporters 1/3 (OAT1/OAT3), organic anion-transporting polypeptide 1B1 (OATP1B1), organic cation transporters 1/2 (OCT1/OCT2), and...

For the elimination of environmental toxins and metabolic waste products, the body is equipped with a range of broad-specificity transporters that are generally present in the liver, kidney, and intestine. The polyspecific organic cation transporters OCT1, 2, and 3 (SLC22A1-3) mediate the facilitated transport of a variety of structurally diverse organic cations, including many drugs, toxins, a...

We quantified, by liquid chromatography tandemmass spectrometry, transporter protein expression of BSEP, MATE1, MRP3, MRP4, NTCP, and OCT1 in our human liver bank (n = 55) and determined the relationship between protein expression and sex, age and genotype. These data complement our previous work in the same liver bank where we quantified the protein expression of OATPs, BCRP, MDR1, and MRP2. I...

Organic cation transporter (OCT) 1could influence an individual’s response to various treatments and increase their susceptibility to diseases. Genotypic and allelic frequencies of nineteen non-synonymous and one intronic Single Nucleotide Polymorphism (SNP) from the OCT1 gene were determined in 101 unrelated healthy Zulu participants, using a SNaPshot multiplex assay. Minor allele frequencies ...