Taiwan cobra phospholipase A2 suppresses ERK-mediated ADAM17 maturation, thus reducing secreted TNF-α production in human leukemia U937 cells

Ying Jung Chen, Hui Chen Lin, Ku Chung Chen, Shinne Ren Lin, Tian Lu Cheng, Long Sen Chang

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The goal of this study was to explore the signaling pathway regulating the processing of proADAM17 into ADAM17 in Taiwan cobra phospholipase A2 (PLA2)-treated human leukemia U937 cells. PLA2 induced reactive oxygen species (ROS)-elicited p38 MAPK activation and ERK inactivation in U937 cells. Catalytically inactive bromophenacylated PLA2 (BPB-PLA2) and PLA2 mutants evoked Ca2+- mediated p38 MAPK activation, and the level of phosphorylated ERK remained unchanged. PLA2 treatment reduced mature ADAM17 expression and secreted TNF-α (sTNF-α) production. Co-treatment of SB202190 (p38 MAPK inhibitor) and catalytically inactive PLA2 increased ERK phosphorylation, ADAM17 maturation and sTNF-α production. Nevertheless, mRNA levels of ADAM17 and TNF-α were insignificantly altered after PLA2 and SB202190/BPB-PLA2 treatment. ADAM17 activity assay and knock-down of ADAM17 revealed that ADAM17 was involved in sTNF-α production. Restoration of ERK activation increased the processing of proADAM17 into ADAM17 in PLA2-treated cells, while inactivation of ERK reduced ADAM17 maturation in untreated and SB202190/BPB-PLA2-treated cells. Removal of cell surface heparan sulfate abrogated PLA2 and SB202190/BPB-PLA2 effect on ADAM17 maturation. Taken together, the present data reveal that PLA2 suppresses ERK-mediated ADAM17 maturation, thus reducing sTNF-α production in U937 cells. Moreover, the binding with heparan sulfate is crucial for the PLA2 effect.

Original languageEnglish
Pages (from-to)79-88
Number of pages10
JournalToxicon
Volume86
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Elapidae
U937 Cells
Phospholipases A2
Taiwan
Leukemia
p38 Mitogen-Activated Protein Kinases
Heparitin Sulfate
Chemical activation
ADAM17 Protein
Cells
Phosphorylation
Processing

Keywords

  • ADAM17
  • ERK
  • Heparan sulfate
  • Post-transcriptional regulation
  • TNF-α

ASJC Scopus subject areas

  • Toxicology
  • Medicine(all)

Cite this

Taiwan cobra phospholipase A2 suppresses ERK-mediated ADAM17 maturation, thus reducing secreted TNF-α production in human leukemia U937 cells. / Chen, Ying Jung; Lin, Hui Chen; Chen, Ku Chung; Lin, Shinne Ren; Cheng, Tian Lu; Chang, Long Sen.

In: Toxicon, Vol. 86, 2014, p. 79-88.

Research output: Contribution to journalArticle

Chen, Ying Jung ; Lin, Hui Chen ; Chen, Ku Chung ; Lin, Shinne Ren ; Cheng, Tian Lu ; Chang, Long Sen. / Taiwan cobra phospholipase A2 suppresses ERK-mediated ADAM17 maturation, thus reducing secreted TNF-α production in human leukemia U937 cells. In: Toxicon. 2014 ; Vol. 86. pp. 79-88.
@article{8aacffb7375041ca91597db7a7905ad3,
title = "Taiwan cobra phospholipase A2 suppresses ERK-mediated ADAM17 maturation, thus reducing secreted TNF-α production in human leukemia U937 cells",
abstract = "The goal of this study was to explore the signaling pathway regulating the processing of proADAM17 into ADAM17 in Taiwan cobra phospholipase A2 (PLA2)-treated human leukemia U937 cells. PLA2 induced reactive oxygen species (ROS)-elicited p38 MAPK activation and ERK inactivation in U937 cells. Catalytically inactive bromophenacylated PLA2 (BPB-PLA2) and PLA2 mutants evoked Ca2+- mediated p38 MAPK activation, and the level of phosphorylated ERK remained unchanged. PLA2 treatment reduced mature ADAM17 expression and secreted TNF-α (sTNF-α) production. Co-treatment of SB202190 (p38 MAPK inhibitor) and catalytically inactive PLA2 increased ERK phosphorylation, ADAM17 maturation and sTNF-α production. Nevertheless, mRNA levels of ADAM17 and TNF-α were insignificantly altered after PLA2 and SB202190/BPB-PLA2 treatment. ADAM17 activity assay and knock-down of ADAM17 revealed that ADAM17 was involved in sTNF-α production. Restoration of ERK activation increased the processing of proADAM17 into ADAM17 in PLA2-treated cells, while inactivation of ERK reduced ADAM17 maturation in untreated and SB202190/BPB-PLA2-treated cells. Removal of cell surface heparan sulfate abrogated PLA2 and SB202190/BPB-PLA2 effect on ADAM17 maturation. Taken together, the present data reveal that PLA2 suppresses ERK-mediated ADAM17 maturation, thus reducing sTNF-α production in U937 cells. Moreover, the binding with heparan sulfate is crucial for the PLA2 effect.",
keywords = "ADAM17, ERK, Heparan sulfate, Post-transcriptional regulation, TNF-α",
author = "Chen, {Ying Jung} and Lin, {Hui Chen} and Chen, {Ku Chung} and Lin, {Shinne Ren} and Cheng, {Tian Lu} and Chang, {Long Sen}",
year = "2014",
doi = "10.1016/j.toxicon.2014.05.012",
language = "English",
volume = "86",
pages = "79--88",
journal = "Toxicon",
issn = "0041-0101",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Taiwan cobra phospholipase A2 suppresses ERK-mediated ADAM17 maturation, thus reducing secreted TNF-α production in human leukemia U937 cells

AU - Chen, Ying Jung

AU - Lin, Hui Chen

AU - Chen, Ku Chung

AU - Lin, Shinne Ren

AU - Cheng, Tian Lu

AU - Chang, Long Sen

PY - 2014

Y1 - 2014

N2 - The goal of this study was to explore the signaling pathway regulating the processing of proADAM17 into ADAM17 in Taiwan cobra phospholipase A2 (PLA2)-treated human leukemia U937 cells. PLA2 induced reactive oxygen species (ROS)-elicited p38 MAPK activation and ERK inactivation in U937 cells. Catalytically inactive bromophenacylated PLA2 (BPB-PLA2) and PLA2 mutants evoked Ca2+- mediated p38 MAPK activation, and the level of phosphorylated ERK remained unchanged. PLA2 treatment reduced mature ADAM17 expression and secreted TNF-α (sTNF-α) production. Co-treatment of SB202190 (p38 MAPK inhibitor) and catalytically inactive PLA2 increased ERK phosphorylation, ADAM17 maturation and sTNF-α production. Nevertheless, mRNA levels of ADAM17 and TNF-α were insignificantly altered after PLA2 and SB202190/BPB-PLA2 treatment. ADAM17 activity assay and knock-down of ADAM17 revealed that ADAM17 was involved in sTNF-α production. Restoration of ERK activation increased the processing of proADAM17 into ADAM17 in PLA2-treated cells, while inactivation of ERK reduced ADAM17 maturation in untreated and SB202190/BPB-PLA2-treated cells. Removal of cell surface heparan sulfate abrogated PLA2 and SB202190/BPB-PLA2 effect on ADAM17 maturation. Taken together, the present data reveal that PLA2 suppresses ERK-mediated ADAM17 maturation, thus reducing sTNF-α production in U937 cells. Moreover, the binding with heparan sulfate is crucial for the PLA2 effect.

AB - The goal of this study was to explore the signaling pathway regulating the processing of proADAM17 into ADAM17 in Taiwan cobra phospholipase A2 (PLA2)-treated human leukemia U937 cells. PLA2 induced reactive oxygen species (ROS)-elicited p38 MAPK activation and ERK inactivation in U937 cells. Catalytically inactive bromophenacylated PLA2 (BPB-PLA2) and PLA2 mutants evoked Ca2+- mediated p38 MAPK activation, and the level of phosphorylated ERK remained unchanged. PLA2 treatment reduced mature ADAM17 expression and secreted TNF-α (sTNF-α) production. Co-treatment of SB202190 (p38 MAPK inhibitor) and catalytically inactive PLA2 increased ERK phosphorylation, ADAM17 maturation and sTNF-α production. Nevertheless, mRNA levels of ADAM17 and TNF-α were insignificantly altered after PLA2 and SB202190/BPB-PLA2 treatment. ADAM17 activity assay and knock-down of ADAM17 revealed that ADAM17 was involved in sTNF-α production. Restoration of ERK activation increased the processing of proADAM17 into ADAM17 in PLA2-treated cells, while inactivation of ERK reduced ADAM17 maturation in untreated and SB202190/BPB-PLA2-treated cells. Removal of cell surface heparan sulfate abrogated PLA2 and SB202190/BPB-PLA2 effect on ADAM17 maturation. Taken together, the present data reveal that PLA2 suppresses ERK-mediated ADAM17 maturation, thus reducing sTNF-α production in U937 cells. Moreover, the binding with heparan sulfate is crucial for the PLA2 effect.

KW - ADAM17

KW - ERK

KW - Heparan sulfate

KW - Post-transcriptional regulation

KW - TNF-α

UR - http://www.scopus.com/inward/record.url?scp=84902208957&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902208957&partnerID=8YFLogxK

U2 - 10.1016/j.toxicon.2014.05.012

DO - 10.1016/j.toxicon.2014.05.012

M3 - Article

C2 - 24874889

AN - SCOPUS:84902208957

VL - 86

SP - 79

EP - 88

JO - Toxicon

JF - Toxicon

SN - 0041-0101

ER -