PubMed · 9379148
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
J C Mohs, W P Newton. 1997. Epidural injections for sciatica.. https://pubmed.ncbi.nlm.nih.gov/9379148/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Sodium-potassium ATPase (Na/K ATPase) is a major target of mineralocorticoids. Both aldosterone and glucocorticoids activate the human Na/K ATPase alpha1 and beta1 genes transcriptionally. The mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) have been shown to bind the glucocorticoid response element (GRE); however, a specific element responsible for the activation of the MR is not known. Sequence analysis of the putative regulatory region of the Na/K ATPase alpha1 gene revealed the presence of a hormone response element that allows the MR to interact with it, at least as well as if not better than the GR. This response element is designated MRE/GRE. In this investigation, we demonstrated the MR and GR induced gene expression in COS-1 cells by cotransfecting with respective expression plasmids (RshMR and RshGR) along with a luciferase reporter. The synthetic MRE/GRE linked to a neutral promoter was activated by MR (6-fold); however, the GR induced a lower level of expression (3.8-fold), suggesting that the element may be preferably MR responsive. Mutations in the synthetic MRE/GRE could not induce the expression with MR, whereas GR had a small effect. Electrophoretic mobility shift analyses demonstrated a direct interaction of MR and GR with the MRE/GRE that was supershifted by an antiMR antibody and the complex was partially cleared by an antiGR antibody, respectively, whereas nonimmune serum had no effect. Footprinting analyses of the promoter region showed that a portion of the DNA containing this element is protected by recombinant MR and GR. Thus these data confirm that this MRE/GRE interacts with both MR and GR but interaction with receptors may be more MR-responsive than response elements previously described.
In this study, we have investigated the effect of altered corticosteroid levels on the expression and processing of the amyloid beta precursor protein (A betaPP) and its amyloid precursor-like protein (APLP) homologue in rat brain. Four groups of animals were used in the study: sham operated, adrenalectomised, and adrenalectomised treated with either dexamethasone or aldosterone, with the A betaPP/APLP expression being determined by western blot analysis. While there were no changes in the levels of A betaPP/APLP following adrenalectomy, treatment with dexamethasone, but not aldosterone, resulted in a marked increase in protein expression levels with the level of increase varying between the brain regions examined. Corticosteroids had a more marked effect on the particulate rather than the soluble form of the protein, thus suggesting that elevated glucocorticoids may also be adversely influencing A betaPP/APLP processing.
Many drugs are now in development for the treatment of atopic diseases, including asthma, allergic rhinitis and atopic dermatitis. These treatments are based on improvements in existing therapies or on a better understanding of the cellular and molecular mechanisms involved in atopic diseases. Although most attention has been focused on asthma, treatments that inhibit the atopic disease process would have application to all atopic diseases, as they often coincide. Most of the many new therapies in development are aimed at inhibiting components of the allergic inflammatory response, but in the future there are real possibilities for the development of preventative and even curative treatments.