PMID- 12547829
OWN - NLM
STAT- MEDLINE
DCOM- 20030519
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 14
DP  - 2003 Apr 4
TI  - Ca2+-independent phospholipase A2 is a novel determinant of store-operated Ca2+ 
      entry.
PG  - 11909-15
AB  - Store-operated cation (SOC) channels and capacitative Ca(2+) entry (CCE) play 
      very important role in cellular function, but the mechanism of their activation 
      remains one of the most intriguing and long lasting mysteries in the field of 
      Ca(2+) signaling. Here, we present the first evidence that Ca(2+)-independent 
      phospholipase A(2) (iPLA(2)) is a crucial molecular determinant in activation of 
      SOC channels and store-operated Ca(2+) entry pathway. Using molecular, imaging, 
      and electrophysiological techniques, we show that directed molecular or 
      pharmacological impairment of the functional activity of iPLA(2) leads to 
      irreversible inhibition of CCE mediated by nonselective SOC channels and by 
      Ca(2+)-release-activated Ca(2+) (CRAC) channels. Transfection of vascular smooth 
      muscle cells (SMC) with antisense, but not sense, oligonucleotides for iPLA(2) 
      impaired thapsigargin (TG)-induced activation of iPLA(2) and TG-induced Ca(2+) 
      and Mn(2+) influx. Identical inhibition of TG-induced Ca(2+) and Mn(2+) influx 
      (but not Ca(2+) release) was observed in SMC, human platelets, and Jurkat 
      T-lymphocytes when functional activity of iPLA(2) was inhibited by its 
      mechanism-based suicidal substrate, bromoenol lactone (BEL). Moreover, 
      irreversible inhibition of iPLA(2) impaired TG-induced activation of single 
      nonselective SOC channels in SMC and BAPTA 
      (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)-induced activation of 
      whole-cell CRAC current in rat basophilic leukemia cells. Thus, functional 
      iPLA(2) is required for activation of store-operated channels and capacitative 
      Ca(2+) influx in wide variety of cell types.
FAU - Smani, Tarik
AU  - Smani T
AD  - Boston University School of Medicine, Boston, Massachusetts 02118, USA.
FAU - Zakharov, Sergey I
AU  - Zakharov SI
FAU - Leno, Endri
AU  - Leno E
FAU - Csutora, Peter
AU  - Csutora P
FAU - Trepakova, Elena S
AU  - Trepakova ES
FAU - Bolotina, Victoria M
AU  - Bolotina VM
LA  - eng
GR  - HL54150/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20030123
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Calcium Channels)
RN  - 0 (Naphthalenes)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Pyrones)
RN  - 42Z2K6ZL8P (Manganese)
RN  - 88070-98-8 (6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Group VI Phospholipases A2)
RN  - EC 3.1.1.4 (PLA2G6 protein, human)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - EC 3.1.1.4 (Pla2g6 protein, mouse)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Aorta/cytology
MH  - Blood Platelets/cytology/*enzymology
MH  - Calcium/*metabolism
MH  - Calcium Channels/*metabolism
MH  - Group VI Phospholipases A2
MH  - Humans
MH  - Jurkat Cells
MH  - Manganese/pharmacokinetics
MH  - Membrane Potentials/drug effects/physiology
MH  - Mice
MH  - Myocytes, Smooth Muscle/cytology/*enzymology
MH  - Naphthalenes/pharmacology
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Patch-Clamp Techniques
MH  - Phosphodiesterase Inhibitors/pharmacology
MH  - Phospholipases A/genetics/*metabolism
MH  - Phospholipases A2
MH  - Pyrones/pharmacology
MH  - Rabbits
MH  - Rats
EDAT- 2003/01/28 04:00
MHDA- 2003/05/20 05:00
CRDT- 2003/01/28 04:00
PHST- 2003/01/28 04:00 [pubmed]
PHST- 2003/05/20 05:00 [medline]
PHST- 2003/01/28 04:00 [entrez]
AID - S0021-9258(19)64774-5 [pii]
AID - 10.1074/jbc.M210878200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Apr 4;278(14):11909-15. doi: 10.1074/jbc.M210878200. Epub 2003 
      Jan 23.