Direkt zum Inhalt
Merck

Hypusination Orchestrates the Antimicrobial Response of Macrophages.

Cell reports (2020-12-17)
Alain P Gobert, Jordan L Finley, Yvonne L Latour, Mohammad Asim, Thaddeus M Smith, Thomas G Verriere, Daniel P Barry, Margaret M Allaman, Alberto G Delagado, Kristie L Rose, M Wade Calcutt, Kevin L Schey, Johanna C Sierra, M Blanca Piazuelo, Raghavendra G Mirmira, Keith T Wilson
ZUSAMMENFASSUNG

Innate responses of myeloid cells defend against pathogenic bacteria via inducible effectors. Deoxyhypusine synthase (DHPS) catalyzes the transfer of the N-moiety of spermidine to the lysine-50 residue of eukaryotic translation initiation factor 5A (EIF5A) to form the amino acid hypusine. Hypusinated EIF5A (EIF5AHyp) transports specific mRNAs to ribosomes for translation. We show that DHPS is induced in macrophages by two gastrointestinal pathogens, Helicobacter pylori and Citrobacter rodentium, resulting in enhanced hypusination of EIF5A. EIF5AHyp was also increased in gastric macrophages from patients with H. pylori gastritis. Furthermore, we identify the bacteria-induced immune effectors regulated by hypusination. This set of proteins includes essential constituents of antimicrobial response and autophagy. Mice with myeloid cell-specific deletion of Dhps exhibit reduced EIF5AHyp in macrophages and increased bacterial burden and inflammation. Thus, regulation of translation through hypusination is a critical hallmark of the defense of eukaryotic hosts against pathogenic bacteria.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
JumpStart Taq-DNA-Polymerase, with MgCl2
Millipore
Protease-Inhibitor-Cocktail-Set III, EDTA-frei, Protease inhibitor cocktail III, EDTA-free for inhibiting aspartic, cysteine, and serine proteases as well as aminopeptidases in mammalian cells and tissues.
Sigma-Aldrich
Monoklonales Anti-β-Aktin in Maus hergestellte Antikörper, clone AC-74, ascites fluid
Sigma-Aldrich
Protease-Inhibitor-Cocktail-Set I, A cocktail of five protease inhibitors that will inhibit a broad range of proteases and esterases. Supplied with a data sheet.
Sigma-Aldrich
PD 98059, PD 98059, CAS 167869-21-8, is a cell-permeable, selective & reversible inhibitor of MAP Kinase Kinase (MEK). Inhibits MAP Kinase activation and subsequent phosphorylation of MAP Kinase substrates.
Sigma-Aldrich
BAY 11-7082, The BAY 11-7082, also referenced under CAS 19542-67-7, controls the biological activity of TNF-α. This small molecule/inhibitor is primarily used for Inflammation/Immunology applications.
Sigma-Aldrich
Anti-iNOS/NOS II-Antikörper, NT, from rabbit, purified by affinity chromatography
Sigma-Aldrich
SB 203580, Hydrochlorid, SB 203580, Hydrochloride, CAS 869185-85-3, is a water-soluble form of SB 203580. A highly potent, selective, ATP-competitive inhibitor of p38 MAP Kinase (IC₅₀ = 34 nM in vitro, 600 nM in cells).