PMID- 23911785
OWN - NLM
STAT- MEDLINE
DCOM- 20131104
LR  - 20161125
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 438
IP  - 3
DP  - 2013 Aug 30
TI  - High glucose induces activation of NF-kappaB inflammatory signaling through IkappaBalpha 
      sumoylation in rat mesangial cells.
PG  - 568-74
LID - S0006-291X(13)01225-4 [pii]
LID - 10.1016/j.bbrc.2013.07.065 [doi]
AB  - The posttranslational modification of proteins by small ubiquitin-like modifiers 
      (SUMOs) has emerged as an important regulatory mechanism for the alteration of 
      protein activity, stability, and cellular localization. The latest research 
      demonstrates that sumoylation is extensively involved in the regulation of the 
      nuclear factor kappaB (NF-kappaB) pathway, which plays a critical role in the regulation 
      of inflammation and contributes to fibrosis in diabetic nephropathy (DN). 
      However, the role of sumoylation in the regulation of NF-kappaB signaling in DN is 
      still unclear. In the present study, we cultured rat glomerular mesangial cells 
      (GMCs) stimulated by high glucose and divided GMCs into six groups: normal 
      glucose group (5.6mmol/L), high glucose groups (10, 20, and 30mmol/L), mannitol 
      group (i.e., osmotic control group), and MG132 intervention group (30mmol/L 
      glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, 
      IkappaBalpha, NF-kappaBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by 
      Western blot, reverse-transcription polymerase chain reaction, and indirect 
      immunofluorescence laser scanning confocal microscopy. The interaction between 
      SUMO1, SUMO2/3, and IkappaBalpha was observed by co-immunoprecipitation. The results 
      showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently 
      enhanced by high glucose (p<0.05). However, the expression of IkappaBalpha sumoylation in 
      high glucose was significantly decreased compared with the normal glucose group 
      (p<0.05). The expression of IkappaBalpha was dose- and time-dependently decreased, and 
      NF-kappaBp65 and MCP-1 were increased under high glucose conditions, which could be 
      mostly reversed by adding MG132 (p<0.05). The present results support the 
      hypothesis that high glucose may activate NF-kappaB inflammatory signaling through 
      IkappaBalpha sumoylation and ubiquitination.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Huang, Wei
AU  - Huang W
AD  - Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, 
      Luzhou, Sichuan 646000, China.
FAU - Xu, Ling
AU  - Xu L
FAU - Zhou, Xueqin
AU  - Zhou X
FAU - Gao, Chenlin
AU  - Gao C
FAU - Yang, Maojun
AU  - Yang M
FAU - Chen, Guo
AU  - Chen G
FAU - Zhu, Jianhua
AU  - Zhu J
FAU - Jiang, Lan
AU  - Jiang L
FAU - Gan, Huakui
AU  - Gan H
FAU - Gou, Fang
AU  - Gou F
FAU - Feng, Hong
AU  - Feng H
FAU - Peng, Juan
AU  - Peng J
FAU - Xu, Yong
AU  - Xu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130802
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Chemokine CCL2)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, rat)
RN  - 0 (SUMO-1 Protein)
RN  - 0 (Transcription Factor RelA)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/biosynthesis
MH  - Diabetic Nephropathies/etiology
MH  - Glucose/*administration & dosage/pharmacology
MH  - I-kappa B Proteins/*metabolism
MH  - Mesangial Cells/*metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*physiology
MH  - Rats
MH  - SUMO-1 Protein/metabolism
MH  - Signal Transduction/drug effects
MH  - Sumoylation/drug effects
MH  - Transcription Factor RelA/biosynthesis
OTO - NOTNLM
OT  - Diabetic nephropathy
OT  - Inflammation
OT  - Nuclear factor kappaB
OT  - Sumoylation
EDAT- 2013/08/06 06:00
MHDA- 2013/11/05 06:00
CRDT- 2013/08/06 06:00
PHST- 2013/07/11 00:00 [received]
PHST- 2013/07/16 00:00 [accepted]
PHST- 2013/08/06 06:00 [entrez]
PHST- 2013/08/06 06:00 [pubmed]
PHST- 2013/11/05 06:00 [medline]
AID - S0006-291X(13)01225-4 [pii]
AID - 10.1016/j.bbrc.2013.07.065 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2013 Aug 30;438(3):568-74. doi: 
      10.1016/j.bbrc.2013.07.065. Epub 2013 Aug 2.