PMID- 28688099
OWN - NLM
STAT- MEDLINE
DCOM- 20180815
LR  - 20181113
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 40
IP  - 5
DP  - 2017 Oct
TI  - Increased O-Linked N-Acetylglucosamine Modification of NF-KappaB and Augmented 
      Cytokine Production in the Placentas from Hyperglycemic Rats.
PG  - 1773-1781
LID - 10.1007/s10753-017-0620-7 [doi]
AB  - Inflammation as a result of NF-kappaB activation may result from the classical 
      (canonical) pathway, with disconnection of the IkappaB inhibitor and subsequent 
      nuclear translocation or, alternatively, by post-translational modifications of 
      modulatory proteins or NF-kappaB subunits (non-canonical pathway). We hypothesized 
      that hyperglycemia-induced increased glycosylation with O-linked 
      N-acetylglucosamine (O-GlcNAc) of NF-kappaB in placental tissue leads to augmented 
      production of pro-inflammatory cytokines, culminating in placental dysfunction 
      and fetal restriction growth. Single injections of streptozotocin (40 mg/kg) or 
      vehicle were used to induce hyperglycemia or normoglycemia, respectively, in 
      female Wistar rats. After 3 days, rats were mated and pregnancy confirmed. 
      Placental tissue was collected at 21 days of pregnancy. Placental expression of 
      p65 subunit was similar between groups. However, nuclear translocation of p65 
      subunit, showing greater activation of NF-kappaB, was increased in the hyperglycemic 
      group. Reduced expression of IkappaB and increased expression of phosphorylated 
      IkappaB(Ser32) were observed in the placenta from hyperglycemic rats, demonstrating 
      increased classical NF-kappaB activation. Augmented modification of O-GlcNAc-modified 
      proteins was found in the placenta from hyperglycemic rats and p65 subunit was a 
      key O-GlcNAc target, as demonstrated by immunoprecipitation. Tumor necrosis 
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expressions were increased in the 
      placenta from hyperglycemic rats. Furthermore, placental weight was increased, 
      whereas fetal weight was decreased under hyperglycemic conditions. TNF-alpha and IL-6 
      demonstrated positive correlations with placental weight and negative 
      correlations with fetal weight and placental efficiency. Therefore, under 
      hyperglycemic conditions, a modulatory role of O-GlcNAc in NF-kappaB activity was 
      demonstrated in the placenta, contributing to fetal and placental dysfunction due 
      to inflammatory cytokine exacerbation.
FAU - Dela Justina, Vanessa
AU  - Dela Justina V
AD  - Institute of Biological Sciences and Health, Federal University of Mato Grosso, 
      Av. Valdon Varjao, Barra do Garcas, MT, 78600-000, Brazil.
FAU - Goncalves, Jessica S
AU  - Goncalves JS
AD  - Institute of Biological Sciences and Health, Federal University of Mato Grosso, 
      Av. Valdon Varjao, Barra do Garcas, MT, 78600-000, Brazil.
FAU - de Freitas, Raiany Alves
AU  - de Freitas RA
AD  - Institute of Biological Sciences and Health, Federal University of Mato Grosso, 
      Av. Valdon Varjao, Barra do Garcas, MT, 78600-000, Brazil.
FAU - Fonseca, Adriany Dias
AU  - Fonseca AD
AD  - Institute of Biological Sciences and Health, Federal University of Mato Grosso, 
      Av. Valdon Varjao, Barra do Garcas, MT, 78600-000, Brazil.
FAU - Volpato, Gustavo T
AU  - Volpato GT
AD  - Institute of Biological Sciences and Health, Federal University of Mato Grosso, 
      Av. Valdon Varjao, Barra do Garcas, MT, 78600-000, Brazil.
FAU - Tostes, Rita C
AU  - Tostes RC
AD  - Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, 
      Brazil.
FAU - Carneiro, Fernando S
AU  - Carneiro FS
AD  - Ribeirao Preto Medical School, University of Sao Paulo, Ribeirao Preto, SP, 
      Brazil.
FAU - Lima, Victor Vitorino
AU  - Lima VV
AD  - Institute of Biological Sciences and Health, Federal University of Mato Grosso, 
      Av. Valdon Varjao, Barra do Garcas, MT, 78600-000, Brazil. vvlima@ufmt.br.
FAU - Giachini, Fernanda R
AU  - Giachini FR
AD  - Institute of Biological Sciences and Health, Federal University of Mato Grosso, 
      Av. Valdon Varjao, Barra do Garcas, MT, 78600-000, Brazil.
LA  - eng
GR  - 151371/2014/Fundacao de Amparo a Pesquisa do Estado de Mato Grosso/
GR  - 211997/2015/Fundacao de Amparo a Pesquisa do Estado de Mato Grosso/
GR  - 23038009165/2013-48/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
GR  - 471675/2013-0/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
GR  - 305823/2015-9/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
GR  - 445777/2014-1/Conselho Nacional de Desenvolvimento Cientifico e Tecnologico/
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - V956696549 (Acetylglucosamine)
SB  - IM
MH  - Acetylglucosamine/*metabolism
MH  - Animals
MH  - Cytokines/*metabolism
MH  - Female
MH  - Fetal Growth Retardation/etiology
MH  - Hyperglycemia/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Placenta/*metabolism/physiopathology
MH  - Pregnancy
MH  - Pregnancy Complications
MH  - Protein Processing, Post-Translational
MH  - Rats
OTO - NOTNLM
OT  - IL-6
OT  - O-GlcNAc
OT  - TNF-alpha
OT  - glycosylation
EDAT- 2017/07/09 06:00
MHDA- 2018/08/16 06:00
CRDT- 2017/07/09 06:00
PHST- 2017/07/09 06:00 [pubmed]
PHST- 2018/08/16 06:00 [medline]
PHST- 2017/07/09 06:00 [entrez]
AID - 10.1007/s10753-017-0620-7 [pii]
AID - 10.1007/s10753-017-0620-7 [doi]
PST - ppublish
SO  - Inflammation. 2017 Oct;40(5):1773-1781. doi: 10.1007/s10753-017-0620-7.