A systems approach to pathways and networks involved in lipid metabolism in macrophage activation
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A systems approach to pathways and networks involved in lipid metabolism in macrophage activation the LIPID MAPS Consortium University Of California San Diego
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A systems approach to pathways and networks involved in lipid metabolism in macrophage activation the LIPID MAPS Consortium University Of California San Diego. Cellular Networks. Signaling Pathways. Gene expression Protein expression Enzyme activation. Lipid Metabolites. Lipid - PowerPoint PPT Presentation
Transcript of A systems approach to pathways and networks involved in lipid metabolism in macrophage activation
A systems approach to pathways and networks involved in lipid
metabolism in macrophage activation
the LIPID MAPS Consortium
University Of California San Diego
Signaling Pathways
Lipid Metabolic Pathways
LipidAssociated
Proteins
LipidMetabolites
Gene expressionProtein expressionEnzyme activation
Cellular Networks
Induction of inflammatory and Induction of inflammatory and immune response genesimmune response genes
Cytokines (IL-1Cytokines (IL-1, TNF, TNF), ), Tissue factor, B7, etc.Tissue factor, B7, etc.
MAP3KMAP3K
(Proteolysis)(Proteolysis)
Macrophage or endothelialMacrophage or endothelial cell membranecell membrane
Direct ActivationDirect Activation
ACTIVATE RAW CELLS WITH
Kdo2-Lipid A
LIPID MAPS
TM
Measure time series of Gene, Lipid, protein and Cytokine Responses
MS MS MS
MS MS MS
MS MS MS
MS MS MS
MS MS MS
MS MS MS
MS MS MS
MS MS MS
MS MS MS
BioReplicates
TechReplicates
Mass SpecRuns
Layers of Replications and Measurements
Lipidomics Data Display : Gene array-search by pathway http://www.lipidmaps.org/data/results/raw2647/microarray/
Lipid Pathways and Networks:Visualization toolsVANTED: Displaying lipidomic timecourse data
http://vanted.ipk-gatersleben.de/
Hyperlink toprotein DB
Hyperlink to lipid DB
Fatty Acids: Omega-9 polyunsaturated and straight chain fatty acids
Integrated lipids, genes, and pathways data across timecourseexperiments for RAW 264.7 cells treated with Kdo2-lipid Awww.lipidmaps.org
LIPID MAPS funded by Glue Grant from:
www.nigms.nih.gov
Fatty Acids: Omega-3 and Omega-6 polyunsaturated fatty acids
Fatty Acids: Eicosanoids
Sterols Glycerophospholipids
Sphingolipids
Overview
PLA
Acetyl CoAcarboxylase
Malo
ny-C
oA
deca
rboxyla
se
Fatty acidsynthase
Carnitine Palmitoyl Transferase (CPT-1)
KDO2-lipid A
DNAcytosol
ACS
mitochondria
Acyltransferases
lipases
PLC
TLR4
Microarray results
Metabolic pathwaySignaling pathway
Energy metabolism
HMG-CoAsynthase
HMG-CoAreductase
Serine Palmitoyltransferase
Rate limiting step
Physical interaction
Sterol O-Acyltransferases
LCAT
LDL HDL
ABCA1 ABCG1
ReceptorsProteins
Lipid rafts
PPAR
Fatty Acid
FAT/CD36 FATP
Malonyl-CoA
Acetyl-CoA
HMG-CoA
Acyl-CoA
Citrate
Acyl-CoACitrate
Sphingolipids
Fatty Acids
Glycerolipids
Glycerophospholipids
SterolsIsoprenoidsCE
2003
Ligand Screen – Time Course
cAMP
0.5’1’
3’8’
20’
PhosphoProtein
2.5’5’
15’30’
MicroArray
30’1 hr
2 hr4 hr
Ca++ 10’
2003
Group Ligand Calcium Cyclic AMP P-Protein Blots Genes Other
Gi S1P ++ + E/A/R SomeSDF ++ + E/A/R SomeBLC ++ + E/A/R SomeELC ++ + E/A/R SomeSLC ++ + E/A/R Some
Gs Terbutaline 0 ++++ 0 SomePGE2 0 ++ (sust) 0 Some
2-MA (?) 0 + 0 Some
Gq & Gs LPA ++ (fast) ++ 0 Some
BCR Antigen ++++ 0 E/A/R Lots Proliferation
IL4 IL4 0 0 Stat 6 Lots
CD40 Anti-CD40 0 0 Delayed E/A/R Lots Proliferation
IL10 IL10 0 0 Stat 3 Yes
BAFF BAFF 0 0 0 Yes Viability
TNF TNFalpha 0 0 0 YesIGF IGF1 0 0 0 YesBOMB BOM 0 0 0 YesfMLP fMLP 0 0 0 YesIFN IFG 0 0 0 YesLeukotriene LTB4 0 0 0 YesNeurokinin NKB 0 0 0NGF NGF 0 0 0 Yes
Summary of Ligand Screen Responses
