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Title: High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells

Abstract

Highlights: •The expression of SUMO1, SUMO2/3 under high glucose was obviously enhanced. •High glucose induced degradation of IκBα and activation of NF-κB pathway. •Sumoylation of IκBα in high glucose were significantly decreased. •The proteasome inhibitor MG132 could partially revert the degradation of IκBα. -- Abstract: 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 κB (NF-κB) 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-κB 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 (5.6 mmol/L), high glucose groups (10, 20, and 30 mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30 mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, andmore » indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and IκBα 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 IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p < 0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 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-κB inflammatory signaling through IκBα sumoylation and ubiquitination.« less

Authors:
 [1];  [1];  [1]; ; ; ; ;  [1];  [2]; ; ;  [1];  [1]
  1. Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000 (China)
  2. Department of Endocrinology, The First Hospital of NeiJiang, Sichuang (China)
Publication Date:
OSTI Identifier:
22242071
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 438; Journal Issue: 3; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; FIBROSIS; GLUCOSE; INFLAMMATION; MONOCYTES; POLYMERASE CHAIN REACTION; PROTEINS; RATS; TIME DEPENDENCE

Citation Formats

Huang, Wei, Department of Endocrinology, The People’s Hospital of Xindu, Xindu, Sichuang, 610500, Xu, Ling, Zhou, Xueqin, Department of Endocrinology, The People’s Hospital of Leshan, Sichuang, Gao, Chenlin, Yang, Maojun, Chen, Guo, Zhu, Jianhua, Jiang, Lan, Gan, Huakui, Gou, Fang, Feng, Hong, Peng, Juan, and Xu, Yong. High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.07.065.
Huang, Wei, Department of Endocrinology, The People’s Hospital of Xindu, Xindu, Sichuang, 610500, Xu, Ling, Zhou, Xueqin, Department of Endocrinology, The People’s Hospital of Leshan, Sichuang, Gao, Chenlin, Yang, Maojun, Chen, Guo, Zhu, Jianhua, Jiang, Lan, Gan, Huakui, Gou, Fang, Feng, Hong, Peng, Juan, & Xu, Yong. High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells. United States. https://doi.org/10.1016/J.BBRC.2013.07.065
Huang, Wei, Department of Endocrinology, The People’s Hospital of Xindu, Xindu, Sichuang, 610500, Xu, Ling, Zhou, Xueqin, Department of Endocrinology, The People’s Hospital of Leshan, Sichuang, Gao, Chenlin, Yang, Maojun, Chen, Guo, Zhu, Jianhua, Jiang, Lan, Gan, Huakui, Gou, Fang, Feng, Hong, Peng, Juan, and Xu, Yong. 2013. "High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells". United States. https://doi.org/10.1016/J.BBRC.2013.07.065.
@article{osti_22242071,
title = {High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells},
author = {Huang, Wei and Department of Endocrinology, The People’s Hospital of Xindu, Xindu, Sichuang, 610500 and Xu, Ling and Zhou, Xueqin and Department of Endocrinology, The People’s Hospital of Leshan, Sichuang and Gao, Chenlin and Yang, Maojun and Chen, Guo and Zhu, Jianhua and Jiang, Lan and Gan, Huakui and Gou, Fang and Feng, Hong and Peng, Juan and Xu, Yong},
abstractNote = {Highlights: •The expression of SUMO1, SUMO2/3 under high glucose was obviously enhanced. •High glucose induced degradation of IκBα and activation of NF-κB pathway. •Sumoylation of IκBα in high glucose were significantly decreased. •The proteasome inhibitor MG132 could partially revert the degradation of IκBα. -- Abstract: 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 κB (NF-κB) 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-κB 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 (5.6 mmol/L), high glucose groups (10, 20, and 30 mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30 mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, 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 IκBα 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 IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p < 0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 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-κB inflammatory signaling through IκBα sumoylation and ubiquitination.},
doi = {10.1016/J.BBRC.2013.07.065},
url = {https://www.osti.gov/biblio/22242071}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 438,
place = {United States},
year = {Fri Aug 30 00:00:00 EDT 2013},
month = {Fri Aug 30 00:00:00 EDT 2013}
}