JNK1/c-Jun and p38α MAPK/ATF-2 pathways are responsible for upregulation of Fas/FasL in human chronic myeloid leukemia K562 cells upon exposure to Taiwan cobra phospholipase A2

Ku Chung Chen, Yi Ling Chiou, Long Sen Chang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Fas and FasL expression upregulation was found in human leukemia K562 cells upon exposure to Naja naja atra phospholipase A2 (PLA2). PLA2 treatment induced an increase in intracellular Ca2+ ([Ca2+]i) and ROS generation levels, leading to activation of p38 MAPK and JNK. Suppression of both p38 MAPK and JNK abrogated Fas and FasL upregulation. Unlike PLA2, catalytically inactive PLA2 treatment did not markedly increase Fas and FasL protein expression, and p38 MAPK activation was exclusively responsible for catalytically inactive PLA 2-induced increase in Fas and FasL protein expression. Knockdown of p38α MAPK and JNK1 by siRNA proved that p38α MAPK and JNK1 were involved in ATF-2 and c-Jun phosphorylation, respectively. Compared with the p38α MAPK/ATF-2 pathway, the JNK1/c-Jun pathway played a crucial role in Fas/FasL upregulation. Unlike arachidonic acid, lysophosphatidylcholine mimicked the PLA2 action in inducing Fas/FasL upregulation. Together with the previous finding that c-Jun and ATF-2 are involved in transcriptional regulation of Fas and FasL, our data suggest that PLA2 induces Fas and FasL upregulation through p38a MAPK/ATF-2 and JNK1/c-Jun pathways in K562 cells, and PLA2 catalytic activity is involved in this action.

Original languageEnglish
Pages (from-to)612-620
Number of pages9
JournalJournal of Cellular Biochemistry
Volume108
Issue number3
DOIs
Publication statusPublished - Oct 15 2009
Externally publishedYes

Fingerprint

Elapidae
K562 Cells
Phospholipases A2
p38 Mitogen-Activated Protein Kinases
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Taiwan
Up-Regulation
Fas Ligand Protein
Chemical activation
Lysophosphatidylcholines
Phosphorylation
Arachidonic Acid
Small Interfering RNA
Catalyst activity
Leukemia

Keywords

  • ATF-2
  • c-Jun
  • Fas/FasL upregulation
  • JNK1
  • p38α MAPK
  • Phospholipase A

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

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title = "JNK1/c-Jun and p38α MAPK/ATF-2 pathways are responsible for upregulation of Fas/FasL in human chronic myeloid leukemia K562 cells upon exposure to Taiwan cobra phospholipase A2",
abstract = "Fas and FasL expression upregulation was found in human leukemia K562 cells upon exposure to Naja naja atra phospholipase A2 (PLA2). PLA2 treatment induced an increase in intracellular Ca2+ ([Ca2+]i) and ROS generation levels, leading to activation of p38 MAPK and JNK. Suppression of both p38 MAPK and JNK abrogated Fas and FasL upregulation. Unlike PLA2, catalytically inactive PLA2 treatment did not markedly increase Fas and FasL protein expression, and p38 MAPK activation was exclusively responsible for catalytically inactive PLA 2-induced increase in Fas and FasL protein expression. Knockdown of p38α MAPK and JNK1 by siRNA proved that p38α MAPK and JNK1 were involved in ATF-2 and c-Jun phosphorylation, respectively. Compared with the p38α MAPK/ATF-2 pathway, the JNK1/c-Jun pathway played a crucial role in Fas/FasL upregulation. Unlike arachidonic acid, lysophosphatidylcholine mimicked the PLA2 action in inducing Fas/FasL upregulation. Together with the previous finding that c-Jun and ATF-2 are involved in transcriptional regulation of Fas and FasL, our data suggest that PLA2 induces Fas and FasL upregulation through p38a MAPK/ATF-2 and JNK1/c-Jun pathways in K562 cells, and PLA2 catalytic activity is involved in this action.",
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author = "Chen, {Ku Chung} and Chiou, {Yi Ling} and Chang, {Long Sen}",
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T1 - JNK1/c-Jun and p38α MAPK/ATF-2 pathways are responsible for upregulation of Fas/FasL in human chronic myeloid leukemia K562 cells upon exposure to Taiwan cobra phospholipase A2

AU - Chen, Ku Chung

AU - Chiou, Yi Ling

AU - Chang, Long Sen

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N2 - Fas and FasL expression upregulation was found in human leukemia K562 cells upon exposure to Naja naja atra phospholipase A2 (PLA2). PLA2 treatment induced an increase in intracellular Ca2+ ([Ca2+]i) and ROS generation levels, leading to activation of p38 MAPK and JNK. Suppression of both p38 MAPK and JNK abrogated Fas and FasL upregulation. Unlike PLA2, catalytically inactive PLA2 treatment did not markedly increase Fas and FasL protein expression, and p38 MAPK activation was exclusively responsible for catalytically inactive PLA 2-induced increase in Fas and FasL protein expression. Knockdown of p38α MAPK and JNK1 by siRNA proved that p38α MAPK and JNK1 were involved in ATF-2 and c-Jun phosphorylation, respectively. Compared with the p38α MAPK/ATF-2 pathway, the JNK1/c-Jun pathway played a crucial role in Fas/FasL upregulation. Unlike arachidonic acid, lysophosphatidylcholine mimicked the PLA2 action in inducing Fas/FasL upregulation. Together with the previous finding that c-Jun and ATF-2 are involved in transcriptional regulation of Fas and FasL, our data suggest that PLA2 induces Fas and FasL upregulation through p38a MAPK/ATF-2 and JNK1/c-Jun pathways in K562 cells, and PLA2 catalytic activity is involved in this action.

AB - Fas and FasL expression upregulation was found in human leukemia K562 cells upon exposure to Naja naja atra phospholipase A2 (PLA2). PLA2 treatment induced an increase in intracellular Ca2+ ([Ca2+]i) and ROS generation levels, leading to activation of p38 MAPK and JNK. Suppression of both p38 MAPK and JNK abrogated Fas and FasL upregulation. Unlike PLA2, catalytically inactive PLA2 treatment did not markedly increase Fas and FasL protein expression, and p38 MAPK activation was exclusively responsible for catalytically inactive PLA 2-induced increase in Fas and FasL protein expression. Knockdown of p38α MAPK and JNK1 by siRNA proved that p38α MAPK and JNK1 were involved in ATF-2 and c-Jun phosphorylation, respectively. Compared with the p38α MAPK/ATF-2 pathway, the JNK1/c-Jun pathway played a crucial role in Fas/FasL upregulation. Unlike arachidonic acid, lysophosphatidylcholine mimicked the PLA2 action in inducing Fas/FasL upregulation. Together with the previous finding that c-Jun and ATF-2 are involved in transcriptional regulation of Fas and FasL, our data suggest that PLA2 induces Fas and FasL upregulation through p38a MAPK/ATF-2 and JNK1/c-Jun pathways in K562 cells, and PLA2 catalytic activity is involved in this action.

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