title: Selenoprotein P neutralizes lipopolysaccharide and participates in hepatic cell endoplasmic reticulum stress response.
abstract: 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.
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, OH, USA.|Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Yongzhong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, OH, USA.
authors.forename: Shuvojit
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, OH, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, OH, USA.
authors.forename: Xinning
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, OH, USA.
authors.forename: Candece L
authors.initials: CL
authors.lastname: Gladson
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, OH, USA.
authors.forename: Warren D
authors.initials: WD
authors.lastname: Heston
authors.affiliation: Department of Cancer Biology, Cleveland Clinic, OH, USA.|Center for Pediatric Infectious Diseases, Cleveland Clinic, OH, USA.
authors.forename: Charles B
authors.initials: CB
authors.lastname: Foster
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression; D006031:Glycosylation / Q000187:drug effects; D057809:HEK293 Cells; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051149:Selenoprotein P / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051140:Selenoproteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D019284:Thapsigargin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C487710:SELENOS protein, human; C043392:SERPINA1 protein, human; D051149:Selenoprotein P; D051140:Selenoproteins; D000515:alpha 1-Antitrypsin; D014415:Tunicamycin; D019284:Thapsigargin
keywords: endoplasmic reticulum stress; histidine-rich peptide; lipopolysaccharide; sepsis; septic shock; systemic inflammatory response syndrome; unfolded protein response