PMID- 18285401
OWN - NLM
STAT- MEDLINE
DCOM- 20080813
LR  - 20131121
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 83
IP  - 5
DP  - 2008 May
TI  - Nitric oxide protects mast cells from activation-induced cell death: the role of 
      the phosphatidylinositol-3 kinase-Akt-endothelial nitric oxide synthase pathway.
PG  - 1218-29
LID - 10.1189/jlb.1007667 [doi]
AB  - NO is known to suppress mast cell activation, but the role of NO in mast cell 
      survival is unclear. Ligation of the high-affinity receptor for IgE (FcepsilonRI) 
      resulted in NO production in mast cells within minutes. This NO production was 
      largely dependent on NO synthase (NOS) activity and extracellular Ca(2+). The NO 
      production required an aggregation of FcepsilonRI and was accompanied by 
      increased phosphorylation of endothelial NOS (eNOS) at Ser1177 and Akt at Ser473. 
      The phosphorylation of eNOS and Akt and the production of NO were abolished by 
      the PI-3K inhibitor wortmannin. Although thapsigargin (TG) induced NO production 
      as well, this response occurred with a considerable lag time (>10 min) and was 
      independent of FcepsilonRI aggregation and PI-3K and NOS activity. Mast cells 
      underwent apoptosis in response to TG but not upon FcepsilonRI ligation. However, 
      when the NOS-dependent NO production was blocked, FcepsilonRI ligation caused 
      sizable apoptosis, substantial mitochondrial cytochrome c release, caspase-3/7 
      activation, and collapse of the mitochondrial membrane potential, all of which 
      were inhibited by the caspase-3 inhibitor z-Asp-Glu-Val-Asp-fluoromethylketone. 
      The data suggest that the NO produced by the PI-3K-Akt-eNOS pathway is involved 
      in protecting mast cells from cell death.
FAU - Inoue, Toshio
AU  - Inoue T
AD  - Division of Molecular Cell Immunology and Allergology, Advanced Medical Research 
      Center, Nihon University Graduate School of Medical Sciences, 30-1 
      Oyaguchikami-cho Itabashi-ku, Tokyo 173-8610, Japan.
FAU - Suzuki, Yoshihiro
AU  - Suzuki Y
FAU - Yoshimaru, Tetsuro
AU  - Yoshimaru T
FAU - Ra, Chisei
AU  - Ra C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080219
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Cell Death
MH  - Cell Line, Tumor
MH  - Cell Survival
MH  - Leukemia, Basophilic, Acute
MH  - Mast Cells/*cytology/enzymology/pathology
MH  - Mitochondria/pathology
MH  - Nitric Oxide/biosynthesis/*physiology
MH  - Nitric Oxide Synthase Type III/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Rats
EDAT- 2008/02/21 09:00
MHDA- 2008/08/14 09:00
CRDT- 2008/02/21 09:00
PHST- 2008/02/21 09:00 [pubmed]
PHST- 2008/08/14 09:00 [medline]
PHST- 2008/02/21 09:00 [entrez]
AID - jlb.1007667 [pii]
AID - 10.1189/jlb.1007667 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2008 May;83(5):1218-29. doi: 10.1189/jlb.1007667. Epub 2008 Feb 
      19.