11beta-Hydroxysteroid dehydrogenase 1 reductase activity is dependent on a high ratio of NADPH/NADP(+) and is stimulated by extracellular glucose
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 97799
Author(s) Amrein, K. E.
Author(s) at UniBasel Odermatt, Alex
Balazs, Zoltan
Nashev, Lyubomir Georgiev
Year 2009
Title 11beta-Hydroxysteroid dehydrogenase 1 reductase activity is dependent on a high ratio of NADPH/NADP(+) and is stimulated by extracellular glucose
Journal Molecular and cellular endocrinology
Volume 301
Number 1-2
Pages / Article-Number 137-41
Keywords 11 beta-Hydroxysteroid dehydrogenase, Glucocorticoid, Glucose, Glucose-6-phosphate, Hexose-6-phosphate dehydrogenase, NADPH
Abstract To assess the impact of the NADPH/NADP(+) ratio and the influence of extracellular glucose on 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) activity, we applied microsomal preparations and intact HEK-293 cells expressing 11beta-HSD1 in the presence or absence of hexose-6-phosphate dehydrogenase (H6PDH). A NADPH/NADP(+) ratio of ten or higher was required for efficient microsomal 11beta-HSD1 reductase activity. Measurements in intact cells suggested that the ER-luminal NADPH concentration is highly sensitive to fluctuating extracellular glucose levels. Lowering glucose in the culture medium dose-dependently decreased 11beta-HSD1 reductase activity and diminished the cortisol/cortisone ratio measured after 24h of incubation. Coexpression with H6PDH potentiated 11beta-HSD1 reductase activity at high glucose. This effect was significantly decreased at low glucose, with concomitantly increased 11beta-HSD1 dehydrogenase activity. In contrast, 11beta-HSD1 reductase activity in H4IIE liver cells and in 3T3-L1 adipocytes was less sensitive to changes in the medium. 11beta-HSD1 dehydrogenase activity was observed in H4IIE cells only at subphysiological glucose levels, indicating a highly efficient supply of substrate for H6PDH and NADPH generation in the ER-lumen. Our results suggest significant cell type-specific differences in ER-luminal NADPH generation that might allow a fine-tuned regulation of glucocorticoid action.
Publisher Elsevier
ISSN/ISBN 0303-7207
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18778749
edoc-URL http://edoc.unibas.ch/dok/A5251920
Full Text on edoc No
Digital Object Identifier DOI 10.1016/j.mce.2008.08.009
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/18778749
ISI-Number 18778749
Document type (ISI) Journal Article
 
   

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