Show simple item record

AuthorMousa, Hanaa
AuthorThanassoulas, Angelos
AuthorZughaier, Susu M
Available date2023-05-04T07:30:08Z
Publication Date2023-07-01
Publication NameBiochemistry and Biophysics Reports
Identifierhttp://dx.doi.org/10.1016/j.bbrep.2023.101445
CitationMousa, H., Thanassoulas, A., & Zughaier, S. M. (2023). ApoM binds endotoxin contributing to neutralization and clearance by High Density Lipoprotein. Biochemistry and Biophysics Reports, 34, 101445.‏
URIhttp://hdl.handle.net/10576/42329
AbstractHDL possesses anti-inflammatory properties, however, the exact mechanism is not fully understood. Endotoxin is a potent inducers of TLR4 signaling, leading to inflammatory mediators' release. It has been estimated that TLR4 recognizes about 5% of circulating lipopolysaccharide whereas 95% is cleared by plasma lipoproteins, mainly HDL. ApoM is required for HDL biogenesis and 95% of plasma ApoM is found associated with HDL, both are significantly reduced during sepsis. The aim of this study is to investigate whether ApoM binds endotoxin and contributes to anti-inflammatory activity of HDL. Isothermal Titration Calorimetry (ITC) was used to determine the binding of ultrapure LPS to the recombinant ApoM protein. Purified human HDL and recombinant ApoM was used to investigate LPS neutralization using human and murine macrophages and computational simulation was performed. ApoM shows high affinity for LPS, forming 1:1 complexes with Kd values below 1 μΜ, as revealed by ITC. The binding process is strongly exothermic and enthalpy-driven (ΔH = -36.5 kJ/mol), implying the formation of an extensive network of interactions between ApoM and LPS in the bound state. Computational simulation also predicted high-affinity binding between ApoM and LPS and the best scoring models showed LPS docking near the calyx of ApoM without blocking the pocket. The biological significance of this interaction was further demonstrated in macrophages where purified HDL neutralized an LPS effect and significantly reduced TNFα release from human THP-1 cells. ApoM binds LPS to facilitate endotoxin neutralization and clearance by HDL.
Languageen
PublisherElsevier
SubjectApoM
Endotoxin
HDL
Isothermal calorimetry
Lipopolysaccharide
Neutralization
TNFα
TitleApoM binds endotoxin contributing to neutralization and clearance by High Density Lipoprotein.
TypeArticle


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record