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Post-Translational Modifications in NETosis and NETs-Mediated Diseases.
Hussein J Hamam1,2, Nades Palaniyar3,4,5
1Program in Translational Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
Biomolecules
|August 17, 2019
Summary
Post-translational modifications (PTMs) of histones regulate neutrophil extracellular trap (NET) formation, impacting diseases. Understanding these histone PTMs is crucial for treating NETosis-related pathologies.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Neutrophils form neutrophil extracellular traps (NETs) to combat pathogens.
- Uncontrolled NET formation (NETosis) contributes to various diseases.
- Histone post-translational modifications (PTMs) critically regulate NETosis.
Purpose of the Study:
- To elucidate the mechanistic details of different NETosis forms.
- To understand the role of histone PTMs in NET formation and neutrophil death.
- To explore the implications of histone PTMs in NET-mediated diseases.
Main Methods:
- Review of recent studies on NETosis mechanisms.
- Analysis of histone modifications (citrullination, methylation, acetylation) in neutrophils.
- Investigation of the role of NADPH oxidase (NOX) and calcium influx in NETosis.
Main Results:
- Histone citrullination promotes rapid, calcium-dependent NETosis, independent of NOX.
- Histone acetylation exhibits a biphasic effect: HDAC inhibitors promote NETosis, while high acetylation suppresses it, favoring apoptosis.
- Histone modifications influence neutrophil survival and death pathways, with implications for diseases like ALI, thrombosis, sepsis, lupus, and cancer.
Conclusions:
- Histone PTMs are key regulators of NETosis and neutrophil fate.
- Histone modifications in NETs can be detrimental, contributing to various pathologies.
- A deeper understanding of histone PTMs in neutrophils is vital for developing treatments for NETosis-driven diseases.
Keywords:
apoptosisepigeneticshistone acetylationhistone citrullinationhistone deacetylase inhibitorshistone methylationneutrophil extracellular trap formationneutrophilspost translational modificationMore Related Videos
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