Absence of hexose-6-phosphate dehydrogenase results in reduced overall glucose consumption but does not prevent 11β-hydroxysteroid dehydrogenase-1-dependent glucocorticoid activation

The FEBS Journal
Philippe MarbetAlex Odermatt

Abstract

Hexose-6-phosphate dehydrogenase (H6PD) is thought to be the major source of NADPH within the endoplasmic reticulum (ER), determining 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) reaction direction to convert inert 11-oxo- to potent 11β-hydroxyglucocorticoids. Here, we tested the hypothesis whether H6pd knock-out (KO) in primary murine bone marrow-derived macrophages results in a switch from 11β-HSD1 oxoreduction to dehydrogenation, thereby inactivating glucocorticoids (GC) and affecting macrophage phenotypic activation as well as causing a more aggressive M1 macrophage phenotype. H6pdKO did not lead to major disturbances of macrophage activation state, although a slightly more pronounced M1 phenotype was observed with enhanced proinflammatory cytokine release, an effect explained by the decreased 11β-HSD1-dependent GC activation. Unexpectedly, ablation of H6pd did not switch 11β-HSD1 reaction direction. A moderately decreased 11β-HSD1 oxoreduction activity by 40-50% was observed in H6pdKO M1 macrophages but dehydrogenation activity was undetectable, providing strong evidence for the existence of an alternative source of NADPH in the ER. H6pdKO M1 activated macrophages showed decreased phagocytic activity, most likely a result...Continue Reading

References

Jan 24, 1977·Biochimica Et Biophysica Acta·S H Hori, T Takahashi
Nov 15, 1987·Archives of Biochemistry and Biophysics·C BublitzS Steavenson
Nov 1, 1967·Clinica Chimica Acta; International Journal of Clinical Chemistry·P L MonteleoneD Y Hsia
Feb 12, 1981·Biochemical and Biophysical Research Communications·C Bublitz
Jun 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J Ozols
Mar 22, 2000·Pathobiology : Journal of Immunopathology, Molecular and Cellular Biology·S GoerdtC E Orfanos
Jun 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·R ThieringerA Hermanowski-Vosatka
Jul 18, 2002·Immunity·Kenneth A FrauwirthCraig B Thompson
Jan 4, 2003·Nature Reviews. Immunology·Siamon Gordon
Feb 9, 2005·Critical Reviews in Clinical Laboratory Sciences·Jan P TuckermannHolger M Reichardt
Jun 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·James S GilmourKaren E Chapman
Oct 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tian Y Zhang, Raymond A Daynes
Nov 20, 2008·Current Protocols in Immunology·Xia ZhangDavid M Mosser
Apr 20, 2010·Molecular and Cellular Endocrinology·Agnes E Coutinho, Karen E Chapman
Aug 9, 2011·Molecular and Cellular Endocrinology·Alex Odermatt, Denise V Kratschmar
Jan 11, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tiina KipariJonathan R Seckl
Feb 26, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Karen E ChapmanJonathan R Seckl
Oct 13, 2016·Cell Reports·Jan Van den BosscheMenno P J de Winther

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.