Possible role of RAC-GTPASE-activating protein in the termination of superoxide production in phagocytic cells

Katalin Szászi, András Korda, Jutta Wölfl, Marie Hélène Paclet, Francoise Morel, E. Ligeti

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The mechanism leading to the termination of superoxide production of phagocytes is poorly understood. The aim of the present study was to investigate the involvement of the active (GTP-bound) form of the GTP-binding proteins in maintaining continuous electron transport through the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. Activation of the enzyme was carried out under in vitro conditions and a shift from the active to the inactive form of the GTP-binding protein was attained (i) by addition of an excess of GDP to the assembled enzyme complex or (ii) by variation of the Rac-GTPase activating (Rac-GAP) capacity of the constituents of the cell-free system. Significant inhibition of O2.-) production was observed when guanine dinucleotides were added after the assembly of the active enzyme complex. The effect was specific for GDP and GDPβS whereas ADP, CDP and UDP were ineffective. GTP was significantly less efficient in inducing superoxide production in a cell-free system containing endogenous GAP activity than in a system devoid of GAP activity. It is suggested that the active, GTP-bound form of Rac is required for sustained catalytic function and Rac-GAP proteins are involved in the downregulation of the oxidase. Copyright (C) 1999 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)764-772
Number of pages9
JournalFree Radical Biology and Medicine
Volume27
Issue number7-8
DOIs
Publication statusPublished - Oct 1999

Fingerprint

Phagocytes
Guanosine Triphosphate
Superoxides
Cell-Free System
GTP-Binding Proteins
Oxidoreductases
rac GTP-Binding Proteins
Enzymes
Cytidine Diphosphate
GTPase-Activating Proteins
Proteins
Enzyme Activation
Uridine Diphosphate
GTP Phosphohydrolases
Guanine
Electron Transport
NADP
Adenosine Diphosphate
Down-Regulation
Chemical activation

Keywords

  • Free radicals
  • GTP-binding proteins
  • GTPase activating proteins
  • NADPH oxidase
  • Neutrophil granulocytes
  • Oproduction
  • Phagocytes
  • Rac

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Possible role of RAC-GTPASE-activating protein in the termination of superoxide production in phagocytic cells. / Szászi, Katalin; Korda, András; Wölfl, Jutta; Paclet, Marie Hélène; Morel, Francoise; Ligeti, E.

In: Free Radical Biology and Medicine, Vol. 27, No. 7-8, 10.1999, p. 764-772.

Research output: Contribution to journalArticle

Szászi, Katalin ; Korda, András ; Wölfl, Jutta ; Paclet, Marie Hélène ; Morel, Francoise ; Ligeti, E. / Possible role of RAC-GTPASE-activating protein in the termination of superoxide production in phagocytic cells. In: Free Radical Biology and Medicine. 1999 ; Vol. 27, No. 7-8. pp. 764-772.
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