Selenoprotein P neutralizes lipopolysaccharide and participates in hepatic cell endoplasmic reticulum stress response

Low serum selenium or selenoprotein P (SePP) levels have been repetitively observed in severe sepsis. The role of SePP in sepsis is incompletely characterized. To test the hypothesis that lipopolysaccharide (LPS) interacts with SePP, we investigated the interaction between LPS and the histidine‐rich...

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Bibliographic Details
Published in:FEBS letters 2016-12, Vol.590 (24), p.4519-4530
Main Authors: Zhao, Yongzhong, Banerjee, Shuvojit, Huang, Ping, Wang, Xinning, Gladson, Candece L., Heston, Warren D., Foster, Charles B.
Format: Article
Language:English
Subjects:
alpha 1-Antitrypsin - genetics
alpha 1-Antitrypsin - metabolism
Amino Acid Sequence
Animals
Conserved Sequence
Endoplasmic Reticulum - drug effects
Endoplasmic Reticulum - metabolism
endoplasmic reticulum stress
Endoplasmic Reticulum Stress - drug effects
Enzyme Inhibitors - pharmacology
Gene Expression
Glycosylation - drug effects
Heat-Shock Proteins - genetics
Heat-Shock Proteins - metabolism
HEK293 Cells
Hep G2 Cells
histidine‐rich peptide
Humans
lipopolysaccharide
Lipopolysaccharides - pharmacology
Liver - cytology
Liver - drug effects
Liver - metabolism
Membrane Proteins - genetics
Membrane Proteins - metabolism
Protein Binding
RNA, Small Interfering - genetics
RNA, Small Interfering - metabolism
Selenoprotein P - agonists
Selenoprotein P - antagonists & inhibitors
Selenoprotein P - genetics
Selenoprotein P - metabolism
Selenoproteins - genetics
Selenoproteins - metabolism
sepsis
septic shock
Sequence Alignment
systemic inflammatory response syndrome
Thapsigargin - pharmacology
Tunicamycin - pharmacology
unfolded protein response
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Summary:Low serum selenium or selenoprotein P (SePP) levels have been repetitively observed in severe sepsis. The role of SePP in sepsis is incompletely characterized. To test the hypothesis that lipopolysaccharide (LPS) interacts with SePP, we investigated the interaction between LPS and the histidine‐rich (His‐rich) regions of SePP. We demonstrate that both purified SePP and synthetic peptides corresponding to the His‐rich motifs neutralized LPS. In addition, we used a hepatocyte model to study the fate of SePP in response to LPS or endoplasmic reticulum (ER) stress. Our findings indicate that ER stress increases the cellular level of SePP and promotes its nuclear localization.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.12494