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EOH Journal Club - Fall 2017 - Shawn Ting

Thursday 11/2 11:00AM - 12:00PM
Bridgeside Point - 339
EOH Journal Club Seminar - Fall 2017

Date: Thursday November 2, 2017

Time: 11am - 12pm

Presenter: Shawn/Hsiu-Chi Ting

Paper:  PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals

Authors: Sally E. Wenzel, Yulia Y. Tyurina, Jinming Zhao, ..., Ivet Bahar, Hulya Bayır, Valerian E. Kagan

Abstract: Ferroptosis is a form of programmed cell death that
is pathogenic to several acute and chronic diseases
and executed via oxygenation of polyunsaturated
phosphatidylethanolamines (PE) by 15-lipoxygenases
(15-LO) that normally use free polyunsaturated
fatty acids as substrates. Mechanisms
of the altered 15-LO substrate specificity are enigmatic.
We sought a common ferroptosis regulator
for 15LO. We discovered that PEBP1, a scaffold
protein inhibitor of protein kinase cascades,
complexes with two 15LO isoforms, 15LO1 and
15LO2, and changes their substrate competence
to generate hydroperoxy-PE. Inadequate reduction
of hydroperoxy-PE due to insufficiency or dysfunction
of a selenoperoxidase, GPX4, leads to
ferroptosis. We demonstrated the importance of
PEBP1-dependent regulatory mechanisms of ferroptotic
death in airway epithelial cells in asthma,
kidney epithelial cells in renal failure, and cortical
and hippocampal neurons in brain trauma. As master
regulators of ferroptotic cell death with profound
implications for human disease, PEBP1/15LO complexes
represent a new target for drug discovery.

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Last Updated On Friday, October 20, 2017 by Orbell, Adam W
Created On Monday, October 02, 2017

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