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Hypusine modification of the ribosome-binding protein eIF5A, a target for new anti-inflammatory drugs: understanding the action of the inhibitor GC7 on a murine macrophage cell line.

Abstract：

:Inflammation is part of an important mechanism triggered by the innate immune response that rapidly responds to invading microorganisms and tissue injury. One important elicitor of the inflammatory response is the Gram-negative bacteria component lipopolysaccharide (LPS), which induces the activation of innate immune response cells, the release of proinflammatory cytokines, such as interleukin 1 and tumor necrosis factor α(TNF-α), and the cellular generation of nitric oxide (NO) by the inducible nitric oxide synthase (iNOS). Although essential to the immune response, uncontrolled inflammatory responses can lead to pathological conditions, such as sepsis and rheumatoid arthritis. Therefore, identifying cellular targets for new anti-inflammatory treatments is crucial to improving therapeutic control of inflammation-related diseases. More recently, the translation factor eIF5A has been demonstrated to have a proinflammatory role in the release of cytokines and the production of NO. As eIF5A requires and essential and unique modification of a specific residue of lysine, changing it to hypusine, eIF5A is an interesting cellular target for anti-inflammatory treatment. The present study reviews the literature concerning the anti-inflammatory effects of inhibiting eIF5A function. We also present new data showing that the inhibition of eIF5A function by the small molecule GC7 significantly decreases TNF-α release without affecting TNF-α mRNA levels. We discuss the mechanisms by which eIF5A may interfere with TNF-α mRNA translation by binding to and regulating the function of ribosomes during protein synthesis.

journal_name

Curr Pharm Des

journal_title

Current pharmaceutical design

authors

de Almeida OP Jr,Toledo TR,Rossi D,Rossetto Dde B,Watanabe TF,Galvão FC,Medeiros AI,Zanelli CF,Valentini SR

doi

10.2174/13816128113199990036

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

284-92

issue

eissn

1381-6128

issn

1873-4286

pii

CPD-EPUB-20130516-12

journal_volume

pub_type

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Hypusine modification of the ribosome-binding protein eIF5A, a target for new anti-inflammatory drugs: understanding the action of the inhibitor GC7 on a murine macrophage cell line.