Compensatory activation of ERK1/2 in Atg5-deficient mouse embryo fibroblasts suppresses oxidative stress-induced cell death

Autophagy
Jong-Ok PyoYong-Keun Jung

Abstract

Despite of the increasing evidence that oxidative stress may induce non-apoptotic cell death or autophagic cell death, the mechanism of this process is unclear. Here, we report a role and a down-stream molecular event of Atg5 during oxidative stress-induced cell death. Compared to wild type (WT) cells, Atg5-deficient mouse embryo fibroblasts (Atg5-/- MEFs) and Atg5 knockdown HT22 neuronal cells were more resistant to cell death induced by H2O2. On the contrary, Atg5-/- MEFs were as sensitive to tumor necrosis factor (TNF)-alpha and cycloheximide as WT cells, and were more sensitive to cell death triggered by amino acid-deprivation than WT MEFs. Treatment with H2O2 induced the recruitment of a GFP-LC3 fusion protein and conversion of LC3 I to LC3 II, correlated with the extent of autophagosome formation in WT cells, but much less in Atg5-deficient cells. Among stress kinases, ERK1/2 was markedly activated in Atg5-/- MEFs and Atg5 knockdown HT22 and SH-SY5Y neuronal cells. The inhibition of ERK1/2 by MEK1 inhibitor (PD98059) or dominant negative ERK2 enhanced the susceptibility of Atg5-/- MEFs to H2O2-induced cell death. Further, reconstitution of Atg5 sensitized Atg5-/- MEFs to H2O2 and suppressed the activation of ERK1/2. These...Continue Reading

Citations

Jul 16, 2010·Journal of Cellular and Molecular Medicine·Michael DewaelePatrizia Agostinis
Feb 4, 2014·Antioxidants & Redox Signaling·Juliana Navarro-YepesRodrigo Franco
Feb 27, 2009·Basic Research in Cardiology·Roberta A GottliebRobert M Mentzer
Apr 16, 2010·Canadian Journal of Physiology and Pharmacology·Yongqiang ChenSpencer B Gibson
Jul 4, 2012·Molecular and Cellular Biology·Philippe WyrschFelix R Althaus
Apr 7, 2020·PloS One·Thiago Nunes RobertoMarcelo Afonso Vallim
Feb 19, 2010·Cellular and Molecular Life Sciences : CMLS·Gian Maria Fimia, Mauro Piacentini
Jul 25, 2013·Antioxidants & Redox Signaling·Kiichi NakahiraStefan W Ryter
May 2, 2009·Cell Death and Differentiation·Y ChenS B Gibson
Oct 2, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yongjun QuanXiaodong Zhang
Apr 7, 2021·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hewang LeePedro A Jose
Jun 3, 2021·International Journal of Molecular Sciences·Jinglong ChenXiaojing Yang

❮ Previous
Next ❯

Related Concepts

Related Feeds

ATG proteins

The discovery of autophagy-related ('ATG') proteins in the 1990s greatly advanced the mechanistic understanding of autophagy and clarified the fact that autophagy serves important roles in various biological processes.

Autophagy Networks

Autophagy is a lysosomal pathway that involves degradation of proteins and functions in normal growth and pathological conditions, through a series of complex networks. The catabolic process involves delivery of proteins and organelles to the lysosome. Here is the latest research on autophagy networks.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Autophagy & Aging: Inhibitors

The feed focuses on the role of nuclear export inhibitors and their effect on autophagy and the aging process.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis