Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human neutrophil granulocytes.
The present study demonstrates the expression of hexose-6-phosphate dehydrogenase and 11 beta-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 11 beta-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.
Kardon
Tamás
T
Semmelweis Egyetem Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézete & MTA-SE Patobiokémiai Kutatócsoport, Budapest, Hungary.
Senesi
Silvia
S
Marcolongo
Paola
P
Legeza
Balázs
B
Bánhegyi
Gábor
G
Mandl
József
J
Fulceri
Rosella
R
Benedetti
Angelo
A
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D000818:Animals; D017209:Apoptosis; D001692:Biological Transport / Q000187:drug effects; D002237:Carbohydrate Dehydrogenases / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D009249:NADP / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats
D009249:NADP; D019298:Glucose-6-Phosphate; D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D006854:Hydrocortisone