PMID- 21953010
OWN - NLM
STAT- MEDLINE
DCOM- 20120612
LR  - 20211020
IS  - 1432-2013 (Electronic)
IS  - 0031-6768 (Linking)
VI  - 463
IP  - 2
DP  - 2012 Feb
TI  - Regulation of Na+/H+ exchanger in dendritic cells by Akt2.
PG  - 355-63
LID - 10.1007/s00424-011-1015-5 [doi]
AB  - Dendritic cells (DCs) are antigen-presenting cells decisive in primary immune 
      responses and establishment of immunological memory. They are activated by 
      bacterial lipopolysaccharides (LPS), which lead to activation of Na(+)/H(+) 
      exchanger activity, cell swelling, reactive oxygen species (ROS) formation, and 
      migration. The effects require functional phosphoinositide 3 kinase and are 
      paralleled by Akt phosphorylation. The present study explored the putative 
      involvement of the Akt isoform Akt2. To this end, experiments were performed in 
      DCs isolated from bone marrow of mice lacking functional Akt2/PKBss (akt2 (-/-)) 
      and respective wild-type animals (akt2 (+/+)). Based on BCECF fluorescence, 
      cytosolic pH (pH(i)) was significantly lower in akt2 (-/-) than in akt2 (+/+) 
      DCs. Transient exposure to NH(4)Cl was followed by profound cytosolic 
      acidification in both genotypes. Subsequent re-alkalinization was largely 
      dependent on Na(+) thus reflecting Na(+)/H(+) exchanger activity and was 
      significantly lower in akt2 (-/-) than in akt2 (+/+) DCs. According to forward 
      scatter in FACS analysis, cell volume was significantly lower in akt2 (-/-) than 
      in akt2 (+/+) DCs. Exposure of DCs to LPS led within 4 h to significant increases 
      of Na(+)/H(+) exchanger activity, cell volume, ROS production, and migration in 
      akt2 (+/+) mice, and its effects were significantly blunted in akt2 (-/-) DCs. 
      The present observations disclose a role of Akt2 in the regulation of pH(i), cell 
      volume, ROS production, and migration in dendritic cells.
FAU - Bhandaru, Madhuri
AU  - Bhandaru M
AD  - Department of Physiology, University of Tubingen, Gmelinstr. 5, 72076, Tubingen, 
      Germany.
FAU - Yang, Wenting
AU  - Yang W
FAU - Rotte, Anand
AU  - Rotte A
FAU - Pasham, Venkanna
AU  - Pasham V
FAU - Lang, Florian
AU  - Lang F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110928
PL  - Germany
TA  - Pflugers Arch
JT  - Pflugers Archiv : European journal of physiology
JID - 0154720
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Cell Size/drug effects
MH  - Cells, Cultured
MH  - Dendritic Cells/cytology/drug effects/*metabolism
MH  - Hydrogen-Ion Concentration
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Proto-Oncogene Proteins c-akt/deficiency/genetics/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Sodium-Hydrogen Exchangers/*metabolism
EDAT- 2011/09/29 06:00
MHDA- 2012/06/13 06:00
CRDT- 2011/09/29 06:00
PHST- 2011/06/22 00:00 [received]
PHST- 2011/08/11 00:00 [accepted]
PHST- 2011/08/10 00:00 [revised]
PHST- 2011/09/29 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2012/06/13 06:00 [medline]
AID - 10.1007/s00424-011-1015-5 [doi]
PST - ppublish
SO  - Pflugers Arch. 2012 Feb;463(2):355-63. doi: 10.1007/s00424-011-1015-5. Epub 2011 
      Sep 28.