Suppression of ERK signaling evokes autocrine fas-mediated death in arachidonic acid-treated human chronic myeloid leukemia K562 cells

Ku Chung Chen, Wen Hsin Liu, Long Sen Chang

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Arachidonic acid (AA)-induced apoptotic death of K562 cells (human chronic myeloid leukemic cells) was characteristic of reactive oxygen species (ROS) generation and mitochondrial depolarization. N-Acetylcysteine pretreatment rescued viability of AA-treated cells and abolished mitochondrial depolarization. In contrast to no significant changes in phospho-JNK and phospho-ERK levels,AAevoked notable activation of p38 MAPK. Unlike that of JNK and p38 MAPK, ERK suppression further reduced the viability of AA-treated cells. Increases in Fas/FasL protein expression, caspase-8 activation, the production of tBid and the loss of mitochondrial membrane potential were noted with K562 cells that were treated with a combination of U0126 and AA. Down-regulation of FADD attenuated U0126-evoked degradation of procaspase-8 and Bid. Abolition of p38 MAPK activation abrogated U0126-elicited Fas/FasL up-regulation in AA-treated cells. U0126 pretreatment suppressed c-Fos phosphorylation but increased p38 MAPK-mediated c-Jun phosphorylation. Knock-down of c-Fos and c-Jun protein expression by siRNA suggested that c-Fos counteracted the effect of c-Jun on Fas/FasL up-regulation. Taken together, our data indicate that AA induces the ROS/mitochondria-dependent death pathway and blocks the ERK pathway which enhances the cytotoxicity of AA through additionally evoking an autocrine Fas-mediated apoptotic mechanism in K562 cells.

Original languageEnglish
Pages (from-to)625-634
Number of pages10
JournalJournal of Cellular Physiology
Volume222
Issue number3
DOIs
Publication statusPublished - Mar 2010
Externally publishedYes

Fingerprint

Autocrine Communication
K562 Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Arachidonic Acid
p38 Mitogen-Activated Protein Kinases
Phosphorylation
Caspase 8
Chemical activation
Cells
Depolarization
Reactive Oxygen Species
Up-Regulation
Proto-Oncogene Proteins c-jun
Mitochondria
Fas Ligand Protein
MAP Kinase Signaling System
Mitochondrial Membrane Potential
Acetylcysteine
Myeloid Cells
Cytotoxicity

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Suppression of ERK signaling evokes autocrine fas-mediated death in arachidonic acid-treated human chronic myeloid leukemia K562 cells. / Chen, Ku Chung; Liu, Wen Hsin; Chang, Long Sen.

In: Journal of Cellular Physiology, Vol. 222, No. 3, 03.2010, p. 625-634.

Research output: Contribution to journalArticle

@article{2db144aa4781485aa82b3a360f14b7c2,
title = "Suppression of ERK signaling evokes autocrine fas-mediated death in arachidonic acid-treated human chronic myeloid leukemia K562 cells",
abstract = "Arachidonic acid (AA)-induced apoptotic death of K562 cells (human chronic myeloid leukemic cells) was characteristic of reactive oxygen species (ROS) generation and mitochondrial depolarization. N-Acetylcysteine pretreatment rescued viability of AA-treated cells and abolished mitochondrial depolarization. In contrast to no significant changes in phospho-JNK and phospho-ERK levels,AAevoked notable activation of p38 MAPK. Unlike that of JNK and p38 MAPK, ERK suppression further reduced the viability of AA-treated cells. Increases in Fas/FasL protein expression, caspase-8 activation, the production of tBid and the loss of mitochondrial membrane potential were noted with K562 cells that were treated with a combination of U0126 and AA. Down-regulation of FADD attenuated U0126-evoked degradation of procaspase-8 and Bid. Abolition of p38 MAPK activation abrogated U0126-elicited Fas/FasL up-regulation in AA-treated cells. U0126 pretreatment suppressed c-Fos phosphorylation but increased p38 MAPK-mediated c-Jun phosphorylation. Knock-down of c-Fos and c-Jun protein expression by siRNA suggested that c-Fos counteracted the effect of c-Jun on Fas/FasL up-regulation. Taken together, our data indicate that AA induces the ROS/mitochondria-dependent death pathway and blocks the ERK pathway which enhances the cytotoxicity of AA through additionally evoking an autocrine Fas-mediated apoptotic mechanism in K562 cells.",
author = "Chen, {Ku Chung} and Liu, {Wen Hsin} and Chang, {Long Sen}",
year = "2010",
month = "3",
doi = "10.1002/jcp.21979",
language = "English",
volume = "222",
pages = "625--634",
journal = "Journal of Cellular Physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Suppression of ERK signaling evokes autocrine fas-mediated death in arachidonic acid-treated human chronic myeloid leukemia K562 cells

AU - Chen, Ku Chung

AU - Liu, Wen Hsin

AU - Chang, Long Sen

PY - 2010/3

Y1 - 2010/3

N2 - Arachidonic acid (AA)-induced apoptotic death of K562 cells (human chronic myeloid leukemic cells) was characteristic of reactive oxygen species (ROS) generation and mitochondrial depolarization. N-Acetylcysteine pretreatment rescued viability of AA-treated cells and abolished mitochondrial depolarization. In contrast to no significant changes in phospho-JNK and phospho-ERK levels,AAevoked notable activation of p38 MAPK. Unlike that of JNK and p38 MAPK, ERK suppression further reduced the viability of AA-treated cells. Increases in Fas/FasL protein expression, caspase-8 activation, the production of tBid and the loss of mitochondrial membrane potential were noted with K562 cells that were treated with a combination of U0126 and AA. Down-regulation of FADD attenuated U0126-evoked degradation of procaspase-8 and Bid. Abolition of p38 MAPK activation abrogated U0126-elicited Fas/FasL up-regulation in AA-treated cells. U0126 pretreatment suppressed c-Fos phosphorylation but increased p38 MAPK-mediated c-Jun phosphorylation. Knock-down of c-Fos and c-Jun protein expression by siRNA suggested that c-Fos counteracted the effect of c-Jun on Fas/FasL up-regulation. Taken together, our data indicate that AA induces the ROS/mitochondria-dependent death pathway and blocks the ERK pathway which enhances the cytotoxicity of AA through additionally evoking an autocrine Fas-mediated apoptotic mechanism in K562 cells.

AB - Arachidonic acid (AA)-induced apoptotic death of K562 cells (human chronic myeloid leukemic cells) was characteristic of reactive oxygen species (ROS) generation and mitochondrial depolarization. N-Acetylcysteine pretreatment rescued viability of AA-treated cells and abolished mitochondrial depolarization. In contrast to no significant changes in phospho-JNK and phospho-ERK levels,AAevoked notable activation of p38 MAPK. Unlike that of JNK and p38 MAPK, ERK suppression further reduced the viability of AA-treated cells. Increases in Fas/FasL protein expression, caspase-8 activation, the production of tBid and the loss of mitochondrial membrane potential were noted with K562 cells that were treated with a combination of U0126 and AA. Down-regulation of FADD attenuated U0126-evoked degradation of procaspase-8 and Bid. Abolition of p38 MAPK activation abrogated U0126-elicited Fas/FasL up-regulation in AA-treated cells. U0126 pretreatment suppressed c-Fos phosphorylation but increased p38 MAPK-mediated c-Jun phosphorylation. Knock-down of c-Fos and c-Jun protein expression by siRNA suggested that c-Fos counteracted the effect of c-Jun on Fas/FasL up-regulation. Taken together, our data indicate that AA induces the ROS/mitochondria-dependent death pathway and blocks the ERK pathway which enhances the cytotoxicity of AA through additionally evoking an autocrine Fas-mediated apoptotic mechanism in K562 cells.

UR - http://www.scopus.com/inward/record.url?scp=73649103090&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73649103090&partnerID=8YFLogxK

U2 - 10.1002/jcp.21979

DO - 10.1002/jcp.21979

M3 - Article

VL - 222

SP - 625

EP - 634

JO - Journal of Cellular Physiology

JF - Journal of Cellular Physiology

SN - 0021-9541

IS - 3

ER -