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Antibacterial and Anti-Inflammatory Effects of Apolipoprotein E

Puthia, Manoj LU ; Marzinek, Jan K. ; Petruk, Ganna LU orcid ; Bergdahl, Gizem Ertürk LU ; Bond, Peter J. and Petrlova, Jitka LU (2022) In Biomedicines 10(6).
Abstract

Apolipoprotein E (APOE) is a lipid-transport protein that functions as a key mediator of lipid transport and cholesterol metabolism. Recent studies have shown that peptides derived from human APOE display anti-inflammatory and antimicrobial effects. Here, we applied in vitro assays and fluorescent microscopy to investigate the anti-bacterial effects of full-length APOE. The interaction of APOE with endotoxins from Escherichia coli was explored using surface plasmon resonance, binding assays, transmission electron microscopy and all-atom molecular dynamics (MD) simulations. We also studied the immunomodulatory activity of APOE using in vitro cell assays and an in vivo mouse model in combination with advanced imaging techniques. We... (More)

Apolipoprotein E (APOE) is a lipid-transport protein that functions as a key mediator of lipid transport and cholesterol metabolism. Recent studies have shown that peptides derived from human APOE display anti-inflammatory and antimicrobial effects. Here, we applied in vitro assays and fluorescent microscopy to investigate the anti-bacterial effects of full-length APOE. The interaction of APOE with endotoxins from Escherichia coli was explored using surface plasmon resonance, binding assays, transmission electron microscopy and all-atom molecular dynamics (MD) simulations. We also studied the immunomodulatory activity of APOE using in vitro cell assays and an in vivo mouse model in combination with advanced imaging techniques. We observed that APOE exhibits anti-bacterial activity against several Gram-negative bacterial strains of Pseudomonas aeruginosa and Escherichia coli. In addition, we showed that APOE exhibits a significant binding affinity for lipopolysaccharide (LPS) and lipid A as well as heparin. MD simulations identified the low-density lipoprotein receptor (LDLR) binding region in helix 4 of APOE as a primary binding site for these molecules via electrostatic interactions. Together, our data suggest that APOE may have an important role in controlling inflammation during Gram-negative bacterial infection.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aggregation, antimicrobial peptides, apolipoprotein E, Gram-negative bacteria, host defense, innate immunity
in
Biomedicines
volume
10
issue
6
article number
1430
publisher
MDPI AG
external identifiers
  • scopus:85132756526
ISSN
2227-9059
DOI
10.3390/biomedicines10061430
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
id
0a5661af-8ede-4b46-b8fe-5d38a5886754
date added to LUP
2025-01-21 15:39:29
date last changed
2025-04-04 14:06:55
@article{0a5661af-8ede-4b46-b8fe-5d38a5886754,
  abstract     = {{<p>Apolipoprotein E (APOE) is a lipid-transport protein that functions as a key mediator of lipid transport and cholesterol metabolism. Recent studies have shown that peptides derived from human APOE display anti-inflammatory and antimicrobial effects. Here, we applied in vitro assays and fluorescent microscopy to investigate the anti-bacterial effects of full-length APOE. The interaction of APOE with endotoxins from Escherichia coli was explored using surface plasmon resonance, binding assays, transmission electron microscopy and all-atom molecular dynamics (MD) simulations. We also studied the immunomodulatory activity of APOE using in vitro cell assays and an in vivo mouse model in combination with advanced imaging techniques. We observed that APOE exhibits anti-bacterial activity against several Gram-negative bacterial strains of Pseudomonas aeruginosa and Escherichia coli. In addition, we showed that APOE exhibits a significant binding affinity for lipopolysaccharide (LPS) and lipid A as well as heparin. MD simulations identified the low-density lipoprotein receptor (LDLR) binding region in helix 4 of APOE as a primary binding site for these molecules via electrostatic interactions. Together, our data suggest that APOE may have an important role in controlling inflammation during Gram-negative bacterial infection.</p>}},
  author       = {{Puthia, Manoj and Marzinek, Jan K. and Petruk, Ganna and Bergdahl, Gizem Ertürk and Bond, Peter J. and Petrlova, Jitka}},
  issn         = {{2227-9059}},
  keywords     = {{aggregation; antimicrobial peptides; apolipoprotein E; Gram-negative bacteria; host defense; innate immunity}},
  language     = {{eng}},
  number       = {{6}},
  publisher    = {{MDPI AG}},
  series       = {{Biomedicines}},
  title        = {{Antibacterial and Anti-Inflammatory Effects of Apolipoprotein E}},
  url          = {{http://dx.doi.org/10.3390/biomedicines10061430}},
  doi          = {{10.3390/biomedicines10061430}},
  volume       = {{10}},
  year         = {{2022}},
}