PMID- 16979159
OWN - NLM
STAT- MEDLINE
DCOM- 20070130
LR  - 20161124
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 549
IP  - 1-3
DP  - 2006 Nov 7
TI  - Involvement of Ca2+-independent phospholipase A2 in the translocation of 
      hypoxia-inducible factor-1alpha to the nucleus under hypoxic conditions.
PG  - 58-62
AB  - We investigated the role of Ca2+-independent phospholipase A2 (iPLA2) as well as 
      cytosolic phospholipase A2 (cPLA2) in hypoxia-inducible factor-1 
      (HIF-1)-dependent gene expression. An inhibitor of both iPLA2 and cPLA2, methyl 
      arachidonyl fluorophosphonate (MAFP), prevented hypoxia-induced erythropoietin 
      mRNA expression without affecting HIF-1alpha accumulation in Hep3B cells. The 
      DNA-binding of HIF-1alpha was suppressed by MAFP as confirmed by luciferase 
      reporter gene assays with the hypoxia response element. Translocation of 
      HIF-1alpha to the nucleus assessed by its presence in the nuclear extracts of 
      cells exposed to hypoxia, was diminished by MAFP. However, hypoxia-dependent gene 
      expression was not affected in mesangial cells obtained from cPLA2alpha null 
      mice. Furthermore, a specific iPLA2 inhibitor, bromoenol lactone, suppressed 
      erythropoietin mRNA expression and HIF-1alpha translocation to the nucleus under 
      hypoxic conditions. Thus, iPLA2, but not cPLA2alpha, may play an important role 
      in regulating the transport of HIF-1alpha to the nucleus.
FAU - Osada-Oka, Mayuko
AU  - Osada-Oka M
AD  - Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Kyoto, 
      Japan.
FAU - Takahashi, Minoru
AU  - Takahashi M
FAU - Akiba, Satoshi
AU  - Akiba S
FAU - Sato, Takashi
AU  - Sato T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060830
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Arachidonic Acids)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Organophosphonates)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (methyl arachidonylfluorophosphonate)
RN  - 11096-26-7 (Erythropoietin)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 3.1.1.32 (Phospholipases A)
RN  - EC 3.1.1.4 (Phospholipases A2)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Animals
MH  - Arachidonic Acids/pharmacology
MH  - Calcium/*metabolism
MH  - Cell Hypoxia/physiology
MH  - Cell Line, Tumor
MH  - Cell Nucleus/drug effects/*metabolism
MH  - Cells, Cultured
MH  - Cytosol/enzymology
MH  - Dose-Response Relationship, Drug
MH  - Erythropoietin/genetics/metabolism
MH  - Gene Expression/genetics
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Immunoblotting
MH  - Luciferases/genetics/metabolism
MH  - Mesangial Cells/cytology/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Organophosphonates/pharmacology
MH  - Phospholipases A/genetics/*metabolism
MH  - Phospholipases A2
MH  - RNA, Messenger/genetics/metabolism
MH  - Recombinant Fusion Proteins/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vascular Endothelial Growth Factor A/genetics/metabolism
EDAT- 2006/09/19 09:00
MHDA- 2007/01/31 09:00
CRDT- 2006/09/19 09:00
PHST- 2006/01/11 00:00 [received]
PHST- 2006/08/12 00:00 [revised]
PHST- 2006/08/18 00:00 [accepted]
PHST- 2006/09/19 09:00 [pubmed]
PHST- 2007/01/31 09:00 [medline]
PHST- 2006/09/19 09:00 [entrez]
AID - S0014-2999(06)00894-6 [pii]
AID - 10.1016/j.ejphar.2006.08.026 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2006 Nov 7;549(1-3):58-62. doi: 10.1016/j.ejphar.2006.08.026. 
      Epub 2006 Aug 30.