PMID- 22178385
OWN - NLM
STAT- MEDLINE
DCOM- 20120510
LR  - 20211021
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1823
IP  - 2
DP  - 2012 Feb
TI  - Peroxiredoxin 6 translocates to the plasma membrane during neutrophil activation 
      and is required for optimal NADPH oxidase activity.
PG  - 306-15
LID - 10.1016/j.bbamcr.2011.11.014 [doi]
AB  - Neutrophils provide the first line of defense against microbial invasion in part 
      through production of reactive oxygen species (ROS) which is mediated through 
      activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 
      generating superoxide anion (O2-). The phagocyte oxidase (phox) has multiple 
      protein components that assemble on the plasma membrane in stimulated 
      neutrophils. We recently described a protein in neutrophils, peroxiredoxin 6 
      (Prdx6), which has both peroxidase and phospholipase A2 (PLA2) activities and 
      enhances oxidase activity in an SDS-activated, cell-free system. The function of 
      Prdx6 in phox activity is further investigated. In reconstituted phox-competent 
      K562 cells, siRNA-mediated suppression of Prdx6 resulted in decreased NADPH 
      oxidase activity in response to formyl-methionyl-leucyl-phenylalanine (fMLP) or 
      phorbol myristate acetate (PMA). In neutrophils stimulated with PMA, Prdx6 
      translocated to plasma membrane as demonstrated by Western blot and confocal 
      microscopy. Translocation of Prdx6 in phox competent K562 cells required both 
      p67phox and p47phox. In addition, plasma membrane from PMA-stimulated, oxidase 
      competent K562 cells with siRNA-mediated Prdx6 suppression contained less p47phox 
      and p67phox compared to cells in which Prdx6 was not decreased. Cell-free oxidase 
      assays showed that recombinant Prdx6 did not alter the Km for NADPH, but 
      increased the Vmax for O2- production in a saturable, Prdx6 
      concentration-dependent manner. Recombinant proteins with mutations in Prdx 
      (C47S) and phospholipase (S32A) activity both enhanced cell-free phox activity to 
      the same extent as wild type protein. Prdx6 supports retention of the active 
      oxidase complex in stimulated plasma membrane, and results with mutant proteins 
      imply that Prdx6 serves an additional biochemical or structural role in 
      supporting optimal NADPH oxidase activity.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Ambruso, Daniel R
AU  - Ambruso DR
AD  - Bonfils Blood Center, Denver, CO 80230, USA. daniel_ambruso@bonfils.org
FAU - Ellison, Michael A
AU  - Ellison MA
FAU - Thurman, Gail W
AU  - Thurman GW
FAU - Leto, Thomas L
AU  - Leto TL
LA  - eng
GR  - K07 HL088968/HL/NHLBI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - P0-CA 46954/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20111208
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Protein Isoforms)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Small Interfering)
RN  - EC 1.11.1.15 (Peroxiredoxin VI)
RN  - EC 1.6.3.- (NADPH Oxidases)
SB  - IM
MH  - Cell Membrane/*metabolism
MH  - Humans
MH  - K562 Cells
MH  - NADPH Oxidases/chemistry/genetics/*metabolism
MH  - *Neutrophil Activation
MH  - Neutrophils/cytology/*metabolism
MH  - Peroxiredoxin VI/genetics/*metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - Protein Subunits/chemistry/genetics/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Transgenes
EDAT- 2011/12/20 06:00
MHDA- 2012/05/11 06:00
CRDT- 2011/12/20 06:00
PHST- 2011/09/26 00:00 [received]
PHST- 2011/11/16 00:00 [revised]
PHST- 2011/11/18 00:00 [accepted]
PHST- 2011/12/20 06:00 [entrez]
PHST- 2011/12/20 06:00 [pubmed]
PHST- 2012/05/11 06:00 [medline]
AID - S0167-4889(11)00316-8 [pii]
AID - 10.1016/j.bbamcr.2011.11.014 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2012 Feb;1823(2):306-15. doi: 10.1016/j.bbamcr.2011.11.014. 
      Epub 2011 Dec 8.