PMID- 16365155
OWN - NLM
STAT- MEDLINE
DCOM- 20060502
LR  - 20201209
IS  - 0741-5400 (Print)
IS  - 0741-5400 (Linking)
VI  - 79
IP  - 3
DP  - 2006 Mar
TI  - Mitochondrial Ca2+ flux is a critical determinant of the Ca2+ dependence of mast 
      cell degranulation.
PG  - 508-18
AB  - An increase in intracellular Ca2+ ([Ca2+]i) is necessary for mast cell 
      exocytosis, but there is controversy over the requirement for Ca2+ in the 
      extracellular medium. Here, we demonstrate that mitochondrial function is a 
      critical determinant of Ca2+ dependence. In the presence of extracellular Ca2+, 
      mitochondrial metabolic inhibitors, including rotenone, antimycin A, and the 
      protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), 
      significantly reduced degranulation induced by immunoglobulin E (IgE) antigen or 
      by thapsigargin, as measured by beta-hexosaminidase release. In the absence of 
      extracellular Ca2+; however, antimycin A and FCCP, but not rotenone, enhanced, 
      rather than reduced, degranulation to a maximum of 76% of that observed in the 
      presence of extracellular Ca2+. This enhancement of extracellular, 
      Ca2+-independent degranulation was concomitant with a rapid collapse of the 
      mitochondrial transmembrane potential. Mitochondrial depolarization did not 
      enhance degranulation induced by thapsigargin, irrespective of the presence or 
      absence of extracellular Ca2+. IgE antigen was more effective than thapsigargin 
      as an inducer of [Ca2+]i release, and mitochondrial depolarization augmented 
      IgE-mediated but not thapsigargin-induced Ca2+ store release and mitochondrial 
      Ca2+ ([Ca2+]m) release. Finally, atractyloside and bongkrekic acid [an agonist 
      and an antagonist, respectively, of the mitochondrial permeability transition 
      pore (mPTP)], respectively, augmented and reduced IgE-mediated Ca2+ store 
      release, [Ca2+]m release, and/or degranulation, whereas they had no effects on 
      thapsigargin-induced Ca2+ store release. These data suggest that the mPTP is 
      involved in the regulation of Ca2+ signaling, thereby affecting the mode of mast 
      cell degranulation. This finding may shed light on a new role for mitochondria in 
      the regulation of mast cell activation.
FAU - Suzuki, Yoshihiro
AU  - Suzuki Y
AD  - Divisionof 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. ysuzuki@med.nihon-u.ac.jp
FAU - Yoshimaru, Tetsuro
AU  - Yoshimaru T
FAU - Inoue, Toshio
AU  - Inoue T
FAU - Ra, Chisei
AU  - Ra C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051219
PL  - England
TA  - J Leukoc Biol
JT  - Journal of leukocyte biology
JID - 8405628
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ion Channels)
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
RN  - 03L9OT429T (Rotenone)
RN  - 11076-19-0 (Bongkrekic Acid)
RN  - 17754-44-8 (Atractyloside)
RN  - 370-86-5 (Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 642-15-9 (Antimycin A)
RN  - 67526-95-8 (Thapsigargin)
RN  - EC 3.2.1.52 (beta-N-Acetylhexosaminidases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Antimycin A/pharmacology
MH  - Atractyloside/pharmacology
MH  - Bongkrekic Acid/pharmacology
MH  - Calcium/*metabolism
MH  - Calcium Signaling/drug effects/*physiology
MH  - Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology
MH  - Cell Degranulation/immunology/*physiology
MH  - Cell Line, Tumor
MH  - Cytoplasmic Granules/drug effects/*metabolism
MH  - Energy Metabolism/drug effects/physiology
MH  - Enzyme Inhibitors/pharmacology
MH  - Extracellular Fluid/drug effects/metabolism
MH  - Immunoglobulin E/immunology/pharmacology
MH  - Ion Channels/drug effects/physiology
MH  - Mast Cells/drug effects/*metabolism
MH  - Membrane Potentials/drug effects/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mitochondria/drug effects/*metabolism
MH  - Mitochondrial Membrane Transport Proteins
MH  - Mitochondrial Permeability Transition Pore
MH  - Rats
MH  - Rotenone/pharmacology
MH  - Thapsigargin/pharmacology
MH  - beta-N-Acetylhexosaminidases/drug effects/metabolism
EDAT- 2005/12/21 09:00
MHDA- 2006/05/04 09:00
CRDT- 2005/12/21 09:00
PHST- 2005/12/21 09:00 [pubmed]
PHST- 2006/05/04 09:00 [medline]
PHST- 2005/12/21 09:00 [entrez]
AID - jlb.0705412 [pii]
AID - 10.1189/jlb.0705412 [doi]
PST - ppublish
SO  - J Leukoc Biol. 2006 Mar;79(3):508-18. doi: 10.1189/jlb.0705412. Epub 2005 Dec 19.