Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells

Lauren Richardson, Christopher Luke Dixon, Leopoldo Aguilera-Aguirre, Ramkumar Menon

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Term and preterm parturition are associated with oxidative stress (OS)-induced p38 mitogen-activated protein kinase (p38MAPK)-mediated fetal tissue (amniochorion) senescence. p38MAPK activation is a complex cell- and stimulant-dependent process. Two independent pathways of OS-induced p38MAPK activation were investigated in amnion epithelial cells (AECs) in response to cigarette smoke extract (CSE: a validated OS inducer in fetal cells): (1) the OS-mediated oxidation of apoptosis signal-regulating kinase (ASK)-1 bound Thioredoxin (Trx[SH]2) dissociates this complex, creating free and activated ASK1-signalosome and (2) transforming growth factor-mediated activation of (TGF)-beta-activated kinase (TAK)1 and TGF-beta-activated kinase 1-binding protein (TAB)1. AECs isolated from normal term, not-in-labor fetal membranes increased p38MAPK in response to CSE and downregulated it in response to antioxidant N-acetylcysteine. In AECs, both Trx and ASK1 were localized; however, they remained dissociated and not complexed, regardless of conditions. Silencing either ASK1 or its downstream effectors (MKK3/6) did not affect OS-induced p38MAPK activation. Conversely, OS increased TGF-beta's release from AECs and increased phosphorylation of both p38MAPK and TAB1. Silencing of TAB1, but not TAK1, prevented p38MAPK activation, which is indicative of TAB1-mediated autophosphorylation of p38MAPK, an activation mechanism seldom seen. OS-induced p38MAPK activation in AECs is ASK1-Trx signalosome-independent and is mediated by the TGF-beta pathway. This knowledge will help to design strategies to reduce p38MAPK activation-associated pregnancy risks.

Original languageEnglish (US)
Pages (from-to)1100-1112
Number of pages13
JournalBiology of Reproduction
Volume99
Issue number5
DOIs
StatePublished - Nov 1 2018

Fingerprint

Amnion
Transforming Growth Factors
p38 Mitogen-Activated Protein Kinases
Oxidative Stress
Epithelial Cells
MAP Kinase Kinase Kinase 5
Extraembryonic Membranes
Thioredoxins
Acetylcysteine
Smoke
Tobacco Products
Carrier Proteins
Fetus
Phosphotransferases
Down-Regulation
Antioxidants
Phosphorylation
Parturition
Pregnancy

Keywords

  • cell culture
  • cytokines
  • labor
  • pregnancy
  • stress

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology

Cite this

Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells. / Richardson, Lauren; Dixon, Christopher Luke; Aguilera-Aguirre, Leopoldo; Menon, Ramkumar.

In: Biology of Reproduction, Vol. 99, No. 5, 01.11.2018, p. 1100-1112.

Research output: Contribution to journalArticle

@article{8025ba3d5e1147c1b22ecc587e38835d,
title = "Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells",
abstract = "Term and preterm parturition are associated with oxidative stress (OS)-induced p38 mitogen-activated protein kinase (p38MAPK)-mediated fetal tissue (amniochorion) senescence. p38MAPK activation is a complex cell- and stimulant-dependent process. Two independent pathways of OS-induced p38MAPK activation were investigated in amnion epithelial cells (AECs) in response to cigarette smoke extract (CSE: a validated OS inducer in fetal cells): (1) the OS-mediated oxidation of apoptosis signal-regulating kinase (ASK)-1 bound Thioredoxin (Trx[SH]2) dissociates this complex, creating free and activated ASK1-signalosome and (2) transforming growth factor-mediated activation of (TGF)-beta-activated kinase (TAK)1 and TGF-beta-activated kinase 1-binding protein (TAB)1. AECs isolated from normal term, not-in-labor fetal membranes increased p38MAPK in response to CSE and downregulated it in response to antioxidant N-acetylcysteine. In AECs, both Trx and ASK1 were localized; however, they remained dissociated and not complexed, regardless of conditions. Silencing either ASK1 or its downstream effectors (MKK3/6) did not affect OS-induced p38MAPK activation. Conversely, OS increased TGF-beta's release from AECs and increased phosphorylation of both p38MAPK and TAB1. Silencing of TAB1, but not TAK1, prevented p38MAPK activation, which is indicative of TAB1-mediated autophosphorylation of p38MAPK, an activation mechanism seldom seen. OS-induced p38MAPK activation in AECs is ASK1-Trx signalosome-independent and is mediated by the TGF-beta pathway. This knowledge will help to design strategies to reduce p38MAPK activation-associated pregnancy risks.",
keywords = "cell culture, cytokines, labor, pregnancy, stress",
author = "Lauren Richardson and Dixon, {Christopher Luke} and Leopoldo Aguilera-Aguirre and Ramkumar Menon",
year = "2018",
month = "11",
day = "1",
doi = "10.1093/biolre/ioy135",
language = "English (US)",
volume = "99",
pages = "1100--1112",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "5",

}

TY - JOUR

T1 - Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells

AU - Richardson, Lauren

AU - Dixon, Christopher Luke

AU - Aguilera-Aguirre, Leopoldo

AU - Menon, Ramkumar

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Term and preterm parturition are associated with oxidative stress (OS)-induced p38 mitogen-activated protein kinase (p38MAPK)-mediated fetal tissue (amniochorion) senescence. p38MAPK activation is a complex cell- and stimulant-dependent process. Two independent pathways of OS-induced p38MAPK activation were investigated in amnion epithelial cells (AECs) in response to cigarette smoke extract (CSE: a validated OS inducer in fetal cells): (1) the OS-mediated oxidation of apoptosis signal-regulating kinase (ASK)-1 bound Thioredoxin (Trx[SH]2) dissociates this complex, creating free and activated ASK1-signalosome and (2) transforming growth factor-mediated activation of (TGF)-beta-activated kinase (TAK)1 and TGF-beta-activated kinase 1-binding protein (TAB)1. AECs isolated from normal term, not-in-labor fetal membranes increased p38MAPK in response to CSE and downregulated it in response to antioxidant N-acetylcysteine. In AECs, both Trx and ASK1 were localized; however, they remained dissociated and not complexed, regardless of conditions. Silencing either ASK1 or its downstream effectors (MKK3/6) did not affect OS-induced p38MAPK activation. Conversely, OS increased TGF-beta's release from AECs and increased phosphorylation of both p38MAPK and TAB1. Silencing of TAB1, but not TAK1, prevented p38MAPK activation, which is indicative of TAB1-mediated autophosphorylation of p38MAPK, an activation mechanism seldom seen. OS-induced p38MAPK activation in AECs is ASK1-Trx signalosome-independent and is mediated by the TGF-beta pathway. This knowledge will help to design strategies to reduce p38MAPK activation-associated pregnancy risks.

AB - Term and preterm parturition are associated with oxidative stress (OS)-induced p38 mitogen-activated protein kinase (p38MAPK)-mediated fetal tissue (amniochorion) senescence. p38MAPK activation is a complex cell- and stimulant-dependent process. Two independent pathways of OS-induced p38MAPK activation were investigated in amnion epithelial cells (AECs) in response to cigarette smoke extract (CSE: a validated OS inducer in fetal cells): (1) the OS-mediated oxidation of apoptosis signal-regulating kinase (ASK)-1 bound Thioredoxin (Trx[SH]2) dissociates this complex, creating free and activated ASK1-signalosome and (2) transforming growth factor-mediated activation of (TGF)-beta-activated kinase (TAK)1 and TGF-beta-activated kinase 1-binding protein (TAB)1. AECs isolated from normal term, not-in-labor fetal membranes increased p38MAPK in response to CSE and downregulated it in response to antioxidant N-acetylcysteine. In AECs, both Trx and ASK1 were localized; however, they remained dissociated and not complexed, regardless of conditions. Silencing either ASK1 or its downstream effectors (MKK3/6) did not affect OS-induced p38MAPK activation. Conversely, OS increased TGF-beta's release from AECs and increased phosphorylation of both p38MAPK and TAB1. Silencing of TAB1, but not TAK1, prevented p38MAPK activation, which is indicative of TAB1-mediated autophosphorylation of p38MAPK, an activation mechanism seldom seen. OS-induced p38MAPK activation in AECs is ASK1-Trx signalosome-independent and is mediated by the TGF-beta pathway. This knowledge will help to design strategies to reduce p38MAPK activation-associated pregnancy risks.

KW - cell culture

KW - cytokines

KW - labor

KW - pregnancy

KW - stress

UR - http://www.scopus.com/inward/record.url?scp=85058774121&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058774121&partnerID=8YFLogxK

U2 - 10.1093/biolre/ioy135

DO - 10.1093/biolre/ioy135

M3 - Article

C2 - 29893818

AN - SCOPUS:85058774121

VL - 99

SP - 1100

EP - 1112

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 5

ER -