PMID- 29208245
OWN - NLM
STAT- MEDLINE
DCOM- 20180720
LR  - 20211204
IS  - 1532-3102 (Electronic)
IS  - 0143-4004 (Linking)
VI  - 60
DP  - 2017 Dec
TI  - Mammalian target of rapamycin signaling is a mechanistic link between increased 
      endoplasmic reticulum stress and autophagy in the placentas of pregnancies 
      complicated by growth restriction.
PG  - 9-20
LID - S0143-4004(17)31130-X [pii]
LID - 10.1016/j.placenta.2017.10.001 [doi]
AB  - INTRODUCTION: Increased endoplasmic reticulum (ER) stress and autophagy have been 
      noted in the placentas of pregnancies complicated by idiopathic intrauterine 
      growth restriction (IUGR); however, the cause of these phenomena remains unclear. 
      We surmised that oxygen-glucose deprivation (OGD) may increase ER stress and 
      autophagy and that mammalian target of rapamycin (mTOR) signaling is involved in 
      regulating placental ER stress and autophagy in pregnancies complicated by IUGR. 
      METHODS: We obtained placentas from women with normal term pregnancies and 
      pregnancies complicated by IUGR to compare ER stress, mTOR signaling, and levels 
      of autophagy-related proteins between the two groups and used primary 
      cytotrophoblast cells treated with or without salubrinal (an ER stress 
      inhibitor), MHY1485 (an mTOR activator), or rapamycin (an mTOR inhibitor) to 
      investigate the effects of OGD on ER stress, mTOR activity, and autophagy levels 
      in vitro. RESULTS: Women with pregnancies complicated by IUGR displayed higher 
      placental ER stress and autophagy levels but lower mTOR activity than women with 
      normal pregnancies. Furthermore, OGD increased ER stress, regulated in 
      development and DNA damage responses-1 (REDD1), phosphorylated tuberous sclerosis 
      complex 2 (TSC2), and autophagy levels and decreased mTOR activity compared to 
      the standard culture condition; however, the salubrinal treatment attenuated 
      these changes. Moreover, the administration of MHY1485 or rapamycin to 
      OGD-treated cells decreased or increased autophagy levels, respectively. 
      DISCUSSION: Based on our results, mTOR is a mechanistic link between OGD-induced 
      ER stress and autophagy in cytotrophoblast cells; thus, mTOR plays an essential 
      role in the pathogenesis of pregnancies complicated by IUGR.
CI  - Copyright (c) 2017 Elsevier Ltd. All rights reserved.
FAU - Hung, Tai-Ho
AU  - Hung TH
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, 
      Taiwan; Department of Chinese Medicine, College of Medicine, Chang Gung 
      University, Taoyuan, Taiwan. Electronic address: thh20@cgmh.org.tw.
FAU - Hsieh, T'sang-T'ang
AU  - Hsieh TT
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, 
      Taiwan.
FAU - Wu, Chung-Pu
AU  - Wu CP
AD  - Graduate Institute of Biomedical Sciences, Department of Physiology and 
      Pharmacology and Molecular Medicine Research Center, College of Medicine, Chang 
      Gung University, Taoyuan, Taiwan; Department of Neurosurgery, Chang Gung Memorial 
      Hospital, Taoyuan, Taiwan.
FAU - Li, Meng-Jen
AU  - Li MJ
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, 
      Taiwan.
FAU - Yeh, Yi-Lin
AU  - Yeh YL
AD  - Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Taipei, 
      Taiwan.
FAU - Chen, Szu-Fu
AU  - Chen SF
AD  - Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, 
      Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20171009
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
RN  - 0 (4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine)
RN  - 0 (Cinnamates)
RN  - 0 (Morpholines)
RN  - 0 (Triazines)
RN  - 0 (salubrinal)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GYV9AM2QAG (Thiourea)
RN  - IY9XDZ35W2 (Glucose)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adult
MH  - *Autophagy
MH  - Cinnamates
MH  - *Endoplasmic Reticulum Stress
MH  - Female
MH  - Fetal Growth Retardation/*metabolism
MH  - Glucose/deficiency
MH  - Humans
MH  - Hypoxia
MH  - Morpholines
MH  - Placenta/*metabolism
MH  - Pregnancy
MH  - Sirolimus
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Thiourea/analogs & derivatives
MH  - Triazines
OTO - NOTNLM
OT  - Autophagy
OT  - Endoplasmic reticulum stress
OT  - Intrauterine growth restriction
OT  - Mammalian target of rapamycin
OT  - Placenta
EDAT- 2017/12/07 06:00
MHDA- 2018/07/22 06:00
CRDT- 2017/12/07 06:00
PHST- 2017/05/12 00:00 [received]
PHST- 2017/10/01 00:00 [revised]
PHST- 2017/10/06 00:00 [accepted]
PHST- 2017/12/07 06:00 [entrez]
PHST- 2017/12/07 06:00 [pubmed]
PHST- 2018/07/22 06:00 [medline]
AID - S0143-4004(17)31130-X [pii]
AID - 10.1016/j.placenta.2017.10.001 [doi]
PST - ppublish
SO  - Placenta. 2017 Dec;60:9-20. doi: 10.1016/j.placenta.2017.10.001. Epub 2017 Oct 9.