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

研究成果: 雜誌貢獻文章

13 引文 (Scopus)

摘要

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.

原文英語
頁(從 - 到)625-634
頁數10
期刊Journal of Cellular Physiology
222
發行號3
DOIs
出版狀態已發佈 - 三月 2010
對外發佈Yes

指紋

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

引用此文

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.

於: Journal of Cellular Physiology, 卷 222, 編號 3, 03.2010, p. 625-634.

研究成果: 雜誌貢獻文章

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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.",
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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.

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