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Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human neutrophil granulocytes
Author(s) -
Kardon Tamás,
Senesi Silvia,
Marcolongo Paola,
Legeza Balázs,
Bánhegyi Gábor,
Mandl József,
Fulceri Rosella,
Benedetti Angelo
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.04.045
Subject(s) - dehydrogenase , endoplasmic reticulum , pentose phosphate pathway , biochemistry , enzyme , glucose 6 phosphate dehydrogenase , granulocyte , chemistry , biology , medicine , glycolysis , immunology
The present study demonstrates the expression of hexose‐6‐phosphate dehydrogenase and 11β‐hydroxysteroid dehydrogenase type 1 in human neutrophils, and the presence and activity of these enzymes in the microsomal fraction of the cells. Their concerted action together with the previously described glucose‐6‐phosphate transporter is responsible for cortisone–cortisol interconversion detected in human neutrophils. Furthermore, the results suggest that luminal NADPH generation by the cortisol dehydrogenase activity of 11β‐hydroxysteroid dehydrogenase type 1 prevents neutrophil apoptosis provoked by the inhibition of the glucose‐6‐phosphate transporter. In conclusion, the maintenance of the luminal NADPH pool is an important antiapoptotic factor in neutrophil granulocytes.