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Leis, HJ; Windischhofer, W.
Calcium-independent phospholipases A2 in murine osteoblastic cells and their inhibition by bromoenol lactone: impact on arachidonate dynamics and prostaglandin synthesis.
J Enzyme Inhib Med Chem. 2016; 31(6):1203-1213 [OPEN ACCESS]
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Autor/innen der Med Uni Graz:
Leis Hans-Jörg
Windischhofer Werner
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Abstract:
Bromoenol lactone (BEL) is an inhibitor of group VI phospholipases (iPLA2s), but has been shown to have severe side effects. iPLA2 characterization in osteoblasts and effect of BEL on prostaglandin (PG) E2 formation. iPLA2 expression: RT-PCR, Western Blotting. PGE2 formation: GC-MS after stimulation, treatment with inhibitors or gene silencing. Arachidonate (AA) reacylation into phospholipids, inhibitor reaction products, PGHS-1 modification proteomic analysis: HR-LC-MS/MS. AA accumulation: (14)C-AA. iPLA2ß and iPLA2γ were expressed and functionally active. BEL inhibition up to 20 μM caused AA accumulation and enhanced PGE2 formation, followed by a decrease at higher concentrations. BEL reacted with intracellular cysteine and GSH leading to GSH depletion and oxidative stress. Initial PGE2 enhancement after BEL inhibition is due to iPLA2-independent accumulation of AA. GSH depletion caused by high BEL concentrations is responsible for the decrease in PGE2 production. BEL must be used with caution in a cellular environment due to conditions of extreme oxidative stress.
Find related publications in this database (using NLM MeSH Indexing)
3T3 Cells -
Animals -
Arachidonic Acid - metabolism
Mice -
Naphthalenes - pharmacology
Osteoblasts - cytology
Osteoblasts - drug effects
Osteoblasts - enzymology
Phospholipases A2, Calcium-Independent - metabolism
Prostaglandins - biosynthesis
Pyrones - pharmacology

Find related publications in this database (Keywords)
Arachidonate release
bromoenol lactone
iPLA2
osteoblast
prostaglandin
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