Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human neutrophil granulocytes

Kardon, Tamás; Senesi, Silvia; Marcolongo, Paola; Legeza, Balázs; Bánhegyi, Gábor; Mandl, József; Fulceri, Rosella; Benedetti, Angelo

doi:10.1016/j.febslet.2008.04.045

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Volume 582, Issue 13 , Pages 1809-1815, 11 June 2008

Maintenance of luminal NADPH in the endoplasmic reticulum promotes the survival of human neutrophil granulocytes

Edited by Robert Barouki

Tamás Kardon
- Semmelweis Egyetem Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézete & MTA-SE Patobiokémiai Kutatócsoport, Budapest, Hungary
- These authors contributed equally to the work.
Silvia Senesi
- Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanità Pubblica, Università di Siena, Viale Aldo Moro 53100, Siena, Italy
- These authors contributed equally to the work.
Paola Marcolongo
- Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanità Pubblica, Università di Siena, Viale Aldo Moro 53100, Siena, Italy
Balázs Legeza
- Semmelweis Egyetem Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézete & MTA-SE Patobiokémiai Kutatócsoport, Budapest, Hungary
Gábor Bánhegyi
- Semmelweis Egyetem Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézete & MTA-SE Patobiokémiai Kutatócsoport, Budapest, Hungary
- Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanità Pubblica, Università di Siena, Viale Aldo Moro 53100, Siena, Italy
- Corresponding author. Address: Dipartimento di Fisiopatologia e, Medicina Sperimentale e Sanità Pubblica, Università di Siena, Viale Aldo Moro 53100, Siena, Italy. Fax: +39 (0)577 234009.
József Mandl
- Semmelweis Egyetem Orvosi Vegytani, Molekuláris Biológiai és Patobiokémiai Intézete & MTA-SE Patobiokémiai Kutatócsoport, Budapest, Hungary
Rosella Fulceri
- Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanità Pubblica, Università di Siena, Viale Aldo Moro 53100, Siena, Italy
Angelo Benedetti
- Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanità Pubblica, Università di Siena, Viale Aldo Moro 53100, Siena, Italy

Received 18 March 2008; received in revised form 21 April 2008; accepted 27 April 2008. published online 08 May 2008.

Abstract

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.

Keywords: Apoptosis, 11β-Hydroxysteroid dehydrogenase type 1, Hexose-6-phosphate dehydrogenase, Glucose-6-phosphate transporter, Glucocorticoid