Gewählte Publikation:
SHR
Neuro
Krebs
Kardio
Lipid
Stoffw
Microb
Dichlberger, A; Schlager, S; Maaninka, K; Schneider, WJ; Kovanen, PT.
Adipose triglyceride lipase regulates eicosanoid production in activated human mast cells.
J Lipid Res. 2014; 55(12):2471-2478
Doi: 10.1194/jlr.M048553
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
-
Schlager Stefanie
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
-
Human mast cells (MCs) contain TG-rich cytoplasmic lipid droplets (LDs) with high arachidonic acid (AA) content. Here, we investigated the functional role of adipose TG lipase (ATGL) in TG hydrolysis and the ensuing release of AA as substrate for eicosanoid generation by activated human primary MCs in culture. Silencing of ATGL in MCs by siRNAs induced the accumulation of neutral lipids in LDs. IgE-dependent activation of MCs triggered the secretion of the two major eicosanoids, prostaglandin D2 (PGD2) and leukotriene C4 (LTC4). The immediate release of PGD2 from the activated MCs was solely dependent on cyclooxygenase (COX) 1, while during the delayed phase of lipid mediator production, the inducible COX-2 also contributed to its release. Importantly, when ATGL-silenced MCs were activated, the secretion of both PGD2 and LTC4 was significantly reduced. Interestingly, the inhibitory effect on the release of LTC4 was even more pronounced in ATGL-silenced MCs than in cytosolic phospholipase A2-silenced MCs. These data show that ATGL hydrolyzes AA-containing TGs present in human MC LDs and define ATGL as a novel regulator of the substrate availability of AA for eicosanoid generation upon MC activation.
Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.
- Find related publications in this database (using NLM MeSH Indexing)
-
Antigens, CD34 - metabolism
-
Arachidonic Acid - metabolism
-
Cells, Cultured -
-
Cyclooxygenase 1 - metabolism
-
Cyclooxygenase 2 - metabolism
-
Eicosanoids - metabolism
-
Gene Silencing -
-
Humans -
-
Immunoglobulin E - metabolism
-
Kinetics -
-
Leukotriene C4 - metabolism
-
Lipase - antagonists & inhibitors
-
Lipase - genetics
-
Lipase - metabolism
-
Lipid Droplets - metabolism
-
Lipolysis -
-
Mast Cells - cytology
-
Mast Cells - immunology
-
Mast Cells - metabolism
-
Phospholipases A2, Cytosolic - antagonists & inhibitors
-
Phospholipases A2, Cytosolic - genetics
-
Phospholipases A2, Cytosolic - metabolism
-
Prostaglandin D2 - metabolism
-
RNA, Small Interfering -
-
Triglycerides - metabolism
- Find related publications in this database (Keywords)
-
arachidonic acid
-
leukotrienes
-
lipid droplets
-
lipolysis and fatty acid metabolism
-
phospholipases
-
A2
-
prostaglandins