Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells†
| Autor: | Leopoldo Aguilera-Aguirre, Ramkumar Menon, Lauren Richardson, Christopher L. Dixon |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine p38 mitogen-activated protein kinases Biology MAP Kinase Kinase Kinase 5 p38 Mitogen-Activated Protein Kinases 03 medical and health sciences Pregnancy Transforming Growth Factor beta Smoke Tobacco TGF beta signaling pathway Humans ASK1 Amnion Phosphorylation RNA Small Interfering Protein kinase A Adaptor Proteins Signal Transducing Kinase Autophosphorylation Epithelial Cells Cell Biology General Medicine MAP Kinase Kinase Kinases Cell biology Enzyme Activation Oxidative Stress 030104 developmental biology Reproductive Medicine Cell culture Female Thioredoxin Research Article |
| Zdroj: | Biol Reprod |
| ISSN: | 1529-7268 0006-3363 |
| DOI: | 10.1093/biolre/ioy135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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