Summary of Study ST001334

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000911. The data can be accessed directly via it's Project DOI: 10.21228/M8XQ28 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001334
Study TitleDeadly Duality of PEBP1: Shutting off Necroptosis, Turning on Ferroptosis
Study TypeObservation study
Study SummaryNecroptosis and ferroptosis are two pathways of regulated cell death executed in several major cardiovascular and neurological acute and degenerative diseases. While the necroptosis program relies on activation of RIP1, RIP3 kinases and MLKL, ferroptotic death is triggered by 15- Lipoxygenase (15LO) catalyzed oxidation of arachidonoyl- (AA) or adrenoyl- (AdA) phosphatidylethanolamines (PE) controlled by the phosphatidylethanolamine-binding protein 1 (PEBP1). PEBP1 displays “regulatory” promiscuity towards multiple protein partners, including RAF1 kinase. Given a distinct structural homology between RAF1 kinase and RIP3 kinase, we hypothesized that PEBP1 may interact with RIP3 and act as a switch from necroptosis to ferroptosis. Using computational, genetic and redox lipidomics approaches, we show that PEBP1 liberated from RAF1 kinase binds and sterically inhibits RIP3 thus turning-off necroptosis. Highly expressed 15LO may outcompete and bind PEBP1 to promote AA-PE/AdA-PE oxidation and ferroptosis. Using cell- based and animal models, we identified the conditions disrupting PEBP1’s interactions with RAF1 kinase to alternatively bind/inhibit RIP3 kinase or bind/activate 15LO. We further established that PEBP1 knockdown sensitizes cells to RIP3-mediated necroptosis. These newly established regulatory functions of PEBP1 serve multiple and diverse roles across various human disease states.
Institute
University of Pittsburgh
Last NameAnthonymuthu
First NameTamil
Address130 desoto street
Emailatamil@pitt.edu
Phone4123837772
Submit Date2020-01-16
Num Groups5
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2020-04-16
Release Version1
Tamil Anthonymuthu Tamil Anthonymuthu
https://dx.doi.org/10.21228/M8XQ28
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000911
Project DOI:doi: 10.21228/M8XQ28
Project Title:Deadly Duality of PEBP1: Shutting off Necroptosis, Turning on Ferroptosis
Project Summary:Lipidomics analysis of mice ileum following irradiation.
Institute:University of Pittsburgh
Last Name:Anthonymuthu
First Name:Tamil
Address:130 Desoto street
Email:atamil@pitt.edu
Phone:4123837772

Subject:

Subject ID:SU001408
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Animal Radiation Duration
SA096725day_1_Control_4_1Control Day 1 irrad
SA096726day_1_Control_4_2Control Day 1 irrad
SA096727day_1_Control_5_1Control Day 1 irrad
SA096728day_1_Control_3_2Control Day 1 irrad
SA096729day_1_Control_1_1Control Day 1 irrad
SA096730day_1_Control_3_1Control Day 1 irrad
SA096731day_1_Control_1_2Control Day 1 irrad
SA096732day_1_Control_2_1Control Day 1 irrad
SA096733day_1_Control_2_2Control Day 1 irrad
SA096734day_1_Control_5_2Control Day 1 irrad
SA096735day_3_Control_2_1Control Day 3 irrad
SA096736day_3_Control_4_2Control Day 3 irrad
SA096737day_3_Control_5_1Control Day 3 irrad
SA096738day_3_Control_5_2Control Day 3 irrad
SA096739day_3_Control_4_1Control Day 3 irrad
SA096740day_3_Control_3_2Control Day 3 irrad
SA096741day_3_Control_2_2Control Day 3 irrad
SA096742day_3_Control_3_1Control Day 3 irrad
SA096743day_3_Control_1_2Control Day 3 irrad
SA096744day_3_Control_1_1Control Day 3 irrad
SA096745day_5_Control_3_1Control Day 5 irrad
SA096746day_5_Control_2_2Control Day 5 irrad
SA096747day_5_Control_2_1Control Day 5 irrad
SA096748day_5_Control_1_2Control Day 5 irrad
SA096749day_5_Control_3_2Control Day 5 irrad
SA096750day_5_Control_1_1Control Day 5 irrad
SA096751day_5_Control_5_2Control Day 5 irrad
SA096752day_5_Control_4_1Control Day 5 irrad
SA096753day_5_Control_5_1Control Day 5 irrad
SA096754day_5_Control_4_2Control Day 5 irrad
SA096755Control_5_1Control No irrad
SA096756Control_4_2Control No irrad
SA096757Control_1_1Control No irrad
SA096758Control_4_1Control No irrad
SA096759Control_5_2Control No irrad
SA096760Control_2_2Control No irrad
SA096761Control_1_2Control No irrad
SA096762Control_2_1Control No irrad
SA096763Control_3_1Control No irrad
SA096764Control_3_2Control No irrad
SA096765day_1_Mutant_4_2Mutant Day 1 irrad
SA096766day_1_Mutant_5_2Mutant Day 1 irrad
SA096767day_1_Mutant_2_1Mutant Day 1 irrad
SA096768day_1_Mutant_1_2Mutant Day 1 irrad
SA096769day_1_Mutant_1_1Mutant Day 1 irrad
SA096770day_1_Mutant_3_1Mutant Day 1 irrad
SA096771day_1_Mutant_2_2Mutant Day 1 irrad
SA096772day_1_Mutant_3_2Mutant Day 1 irrad
SA096773day_1_Mutant_5_1Mutant Day 1 irrad
SA096774day_1_Mutant_4_1Mutant Day 1 irrad
SA096775day_3_Mutant_4_2Mutant Day 3 irrad
SA096776day_3_Mutant_5_1Mutant Day 3 irrad
SA096777day_3_Mutant_5_2Mutant Day 3 irrad
SA096778day_3_Mutant_4_1Mutant Day 3 irrad
SA096779day_3_Mutant_1_1Mutant Day 3 irrad
SA096780day_3_Mutant_3_2Mutant Day 3 irrad
SA096781day_3_Mutant_2_1Mutant Day 3 irrad
SA096782day_3_Mutant_1_2Mutant Day 3 irrad
SA096783day_3_Mutant_2_2Mutant Day 3 irrad
SA096784day_3_Mutant_3_1Mutant Day 3 irrad
SA096785day_5_Mutant_3_1Mutant Day 5 irrad
SA096786day_5_Mutant_2_2Mutant Day 5 irrad
SA096787day_5_Mutant_1_1Mutant Day 5 irrad
SA096788day_5_Mutant_3_2Mutant Day 5 irrad
SA096789day_5_Mutant_1_2Mutant Day 5 irrad
SA096790day_5_Mutant_5_1Mutant Day 5 irrad
SA096791day_5_Mutant_5_2Mutant Day 5 irrad
SA096792day_5_Mutant_4_1Mutant Day 5 irrad
SA096793day_5_Mutant_2_1Mutant Day 5 irrad
SA096794day_5_Mutant_4_2Mutant Day 5 irrad
SA096795Mutant_5_1Mutant No irrad
SA096796Mutant_4_1Mutant No irrad
SA096797Mutant_1_2Mutant No irrad
SA096798Mutant_1_1Mutant No irrad
SA096799Mutant_5_2Mutant No irrad
SA096800Mutant_2_1Mutant No irrad
SA096801Mutant_2_2Mutant No irrad
SA096802Mutant_3_2Mutant No irrad
SA096803Mutant_3_1Mutant No irrad
SA096804Mutant_4_2Mutant No irrad
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Collection:

Collection ID:CO001403
Collection Summary:At the time of sacrifice animals were transcardially perfused with 5 ml phosphate buffered saline (PBS) and ileum was snap frozen.
Sample Type:Ileum

Treatment:

Treatment ID:TR001423
Treatment Summary:Mice were anaesthetized with Nembutal (50 mg/kg) and irradiated to 9.25Gy using a Shepherd Mark 1 Model 68 cesium irradiator at a dose rate of 80 cGy/minute, as described (Huang et al., 2016).

Sample Preparation:

Sampleprep ID:SP001416
Sampleprep Summary:Total Lipid Extraction. Lipids were extracted from using the Folch method (Folch et al., 1957). Total phospholipid content was quantified using the micro method for phosphorus measurement (Böttcher et al., 1961). Tissue CL and PE content was quantified as described previously (Wenzel et al., 2017).
Processing Storage Conditions:-80℃
Extract Storage:-80℃

Combined analysis:

Analysis ID AN002223
Analysis type MS
Chromatography type Reversed phase
Chromatography system Thermo Dionex Ultimate 3000 RS
Column Luna C18 (150 x 4.6mm,3um,100Å)
MS Type ESI
MS instrument type Orbitrap
MS instrument name Thermo Q Exactive Plus Orbitrap
Ion Mode NEGATIVE
Units Normalized amount

Chromatography:

Chromatography ID:CH001631
Instrument Name:Thermo Dionex Ultimate 3000 RS
Column Name:Luna C18 (150 x 4.6mm,3um,100Å)
Chromatography Type:Reversed phase

MS:

MS ID:MS002069
Analysis ID:AN002223
Instrument Name:Thermo Q Exactive Plus Orbitrap
Instrument Type:Orbitrap
MS Type:ESI
MS Comments:Compound discoverer
Ion Mode:NEGATIVE
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