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
N1 - Funding Information:
1Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch, Galveston, Texas, USA and 2Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, Tx, 77550 ∗Correspondence: Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Perinatal Research, The University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-1062, USA. Tel: +409-772-7596; Fax: +409-747-0475; E-mail: ram.menon@utmb.edu †Grant Support: This study is supported by the Innovative Catalyst Grant from March of Dimes Ohio Center, Cincinnati, Ohio (NIH/NICHD R03HD067446) to RM. Conference Presentation: This manuscript was presented in part at the 64th Annual Meeting of the Society for Reproductive Investigation, March 2017. Data availability: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Edited by Dr. Myriam Hemberger, PhD, Babraham Institute
Funding Information:
This study is supported by the Innovative Catalyst Grant from March of Dimes Ohio Center, Cincinnati, Ohio (NIH/NICHD R03HD067446) to RM.
Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction.
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
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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 -