Antimicrobial peptide epinecidin-1 modulates MyD88 protein levels via the proteasome degradation pathway

Bor Chyuan Su, Jyh Yih Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1. Our results demonstrate that epinecidin-1 alone does not affect A20, IRAK-M, or SOCS-1 protein levels. However, pre-incubation of epinecidin-1 significantly inhibits LPS-induced upregulation of A20, IRAK-M, and SOCS-1. In addition, epinecidin-1 significantly reduces the abundance of MyD88 protein. Both MG132 (a specific proteasome inhibitor) and Heclin (a specific Smurf E3 ligase inhibitor) are able to abolish epinecidin-1-mediated MyD88 degradation. Thus, our data suggest that epinecidin-1 directly inhibits MyD88 via induction of the Smurf E3 ligase proteasome pathway.

Original languageEnglish
Article number362
JournalMarine Drugs
Volume15
Issue number11
DOIs
Publication statusPublished - Nov 1 2017
Externally publishedYes

Fingerprint

Myeloid Differentiation Factor 88
Interleukin-1 Receptor-Associated Kinases
Proteasome Endopeptidase Complex
Lipopolysaccharides
Peptides
Ubiquitin-Protein Ligases
Toll-Like Receptors
Antimicrobial Cationic Peptides
Cytokines
Toll-Like Receptor 4
Proteasome Inhibitors
Up-Regulation
Inflammation
Neoplasms

Keywords

  • A20
  • Epinecidin-1
  • IRAK-M
  • MyD88
  • Proteasome
  • SOCS-1

ASJC Scopus subject areas

  • Drug Discovery

Cite this

Antimicrobial peptide epinecidin-1 modulates MyD88 protein levels via the proteasome degradation pathway. / Su, Bor Chyuan; Chen, Jyh Yih.

In: Marine Drugs, Vol. 15, No. 11, 362, 01.11.2017.

Research output: Contribution to journalArticle

@article{5201797aa01a4f4bbad2ccc10b380f21,
title = "Antimicrobial peptide epinecidin-1 modulates MyD88 protein levels via the proteasome degradation pathway",
abstract = "The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1. Our results demonstrate that epinecidin-1 alone does not affect A20, IRAK-M, or SOCS-1 protein levels. However, pre-incubation of epinecidin-1 significantly inhibits LPS-induced upregulation of A20, IRAK-M, and SOCS-1. In addition, epinecidin-1 significantly reduces the abundance of MyD88 protein. Both MG132 (a specific proteasome inhibitor) and Heclin (a specific Smurf E3 ligase inhibitor) are able to abolish epinecidin-1-mediated MyD88 degradation. Thus, our data suggest that epinecidin-1 directly inhibits MyD88 via induction of the Smurf E3 ligase proteasome pathway.",
keywords = "A20, Epinecidin-1, IRAK-M, MyD88, Proteasome, SOCS-1",
author = "Su, {Bor Chyuan} and Chen, {Jyh Yih}",
year = "2017",
month = "11",
day = "1",
doi = "10.3390/md15110362",
language = "English",
volume = "15",
journal = "Marine Drugs",
issn = "1660-3397",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "11",

}

TY - JOUR

T1 - Antimicrobial peptide epinecidin-1 modulates MyD88 protein levels via the proteasome degradation pathway

AU - Su, Bor Chyuan

AU - Chen, Jyh Yih

PY - 2017/11/1

Y1 - 2017/11/1

N2 - The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1. Our results demonstrate that epinecidin-1 alone does not affect A20, IRAK-M, or SOCS-1 protein levels. However, pre-incubation of epinecidin-1 significantly inhibits LPS-induced upregulation of A20, IRAK-M, and SOCS-1. In addition, epinecidin-1 significantly reduces the abundance of MyD88 protein. Both MG132 (a specific proteasome inhibitor) and Heclin (a specific Smurf E3 ligase inhibitor) are able to abolish epinecidin-1-mediated MyD88 degradation. Thus, our data suggest that epinecidin-1 directly inhibits MyD88 via induction of the Smurf E3 ligase proteasome pathway.

AB - The cationic antimicrobial peptide epinecidin-1 was identified from Epinephelus coioides and possesses multiple biological functions, including antibacterial, antifungal, anti-tumor, and immunomodulatory effects. In addition, epinecidin-1 suppresses lipopolysaccharide (LPS)-induced inflammation by neutralizing LPS and ameliorating LPS/Toll-like receptor (TLR)-4 internalization. However, it is unclear whether the actions of epinecidin-1 depend on the regulation of TLR adaptor protein MyD88 or endogenous TLR signaling antagonists, which include A20, interleukin-1 receptor associated kinase (IRAK)-M, and suppressor of cytokine signaling (SOCS)-1. Our results demonstrate that epinecidin-1 alone does not affect A20, IRAK-M, or SOCS-1 protein levels. However, pre-incubation of epinecidin-1 significantly inhibits LPS-induced upregulation of A20, IRAK-M, and SOCS-1. In addition, epinecidin-1 significantly reduces the abundance of MyD88 protein. Both MG132 (a specific proteasome inhibitor) and Heclin (a specific Smurf E3 ligase inhibitor) are able to abolish epinecidin-1-mediated MyD88 degradation. Thus, our data suggest that epinecidin-1 directly inhibits MyD88 via induction of the Smurf E3 ligase proteasome pathway.

KW - A20

KW - Epinecidin-1

KW - IRAK-M

KW - MyD88

KW - Proteasome

KW - SOCS-1

UR - http://www.scopus.com/inward/record.url?scp=85036505959&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85036505959&partnerID=8YFLogxK

U2 - 10.3390/md15110362

DO - 10.3390/md15110362

M3 - Article

C2 - 29144391

AN - SCOPUS:85036505959

VL - 15

JO - Marine Drugs

JF - Marine Drugs

SN - 1660-3397

IS - 11

M1 - 362

ER -