Next Article in Journal
Oxidation of 5-methylaminomethyl uridine (mnm5U) by Oxone Leads to Aldonitrone Derivatives
Next Article in Special Issue
Combining Optical Approaches with Human Inducible Pluripotent Stem Cells in G Protein-Coupled Receptor Drug Screening and Development
Previous Article in Journal
Exploring Solanum tuberosum Epoxide Hydrolase Internal Architecture by Water Molecules Tracking
Previous Article in Special Issue
Single Molecule FRET: A Powerful Tool to Study Intrinsically Disordered Proteins
Article Menu
Issue 4 (December) cover image

Export Article

Open AccessArticle
Biomolecules 2018, 8(4), 144; https://doi.org/10.3390/biom8040144

Furanoid F-Acid F6 Uniquely Induces NETosis Compared to C16 and C18 Fatty Acids in Human Neutrophils

1
Program in Translational Medicine, Peter Gilgan Centre for Research and Learning, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
2
Department of Pharmacology, University of Toronto, Toronto, ON M5S 1A8, Canada
3
Department of Biological Sciences, Faculty of Science, Kuwait University, Safat 13060, Kuwait
4
Department of Zoology, CMS College, Kottayam 686001, India
5
Departments of Lab Medicine and Pathobiology, and Institute of Medical Sciences, Faculty of Medicine, University of Toronto, Toronto, ON M5G 0A4, Canada
*
Author to whom correspondence should be addressed.
Received: 28 August 2018 / Revised: 7 November 2018 / Accepted: 7 November 2018 / Published: 13 November 2018
Full-Text   |   PDF [3624 KB, uploaded 19 November 2018]   |  

Abstract

Various biomolecules induce neutrophil extracellular trap (NET) formation or NETosis. However, the effect of fatty acids on NETosis has not been clearly established. In this study, we focused on the NETosis-inducing ability of several lipid molecules. We extracted the lipid molecules present in Arabian Gulf catfish (Arius bilineatus, Val) skin gel, which has multiple therapeutic activities. Gas chromatography–mass spectrometry (GC-MS) analysis of the lipid fraction-3 from the gel with NETosis-inducing activity contained fatty acids including a furanoid F-acid (F6; 12,15-epoxy-13,14-dimethyleicosa-12,14-dienoic acid) and common long-chain fatty acids such as palmitic acid (PA; C16:0), palmitoleic acid (PO; C16:1), stearic acid (SA; C18:0), and oleic acid (OA; C18:1). Using pure molecules, we show that all of these fatty acids induce NETosis to different degrees in a dose-dependent fashion. Notably, F6 induces a unique form of NETosis that is rapid and induces reactive oxygen species (ROS) production by both NADPH oxidase (NOX) and mitochondria. F6 also induces citrullination of histone. By contrast, the common fatty acids (PA, PO, SA, and OA) only induce NOX-dependent NETosis. The activation of the kinases such as ERK (extracellular signal-regulated kinase) and JNK (c-Jun N-terminal kinase) is important for long-chain fatty acid-induced NETosis, whereas, in F-acid-induced NETosis, Akt is additionally needed. Nevertheless, NETosis induced by all of these compounds requires the final chromatin decondensation step of transcriptional firing. These findings are useful for understanding F-acid- and other fatty acid-induced NETosis and to establish the active ingredients with therapeutic potential for regulating diseases involving NET formation. View Full-Text
Keywords: furanoid F-acids (F6); catfish lipids; long-chain fatty acids; NETosis; NADPH oxidase; ROS; MAP kinases; citrullination of histone; transcription furanoid F-acids (F6); catfish lipids; long-chain fatty acids; NETosis; NADPH oxidase; ROS; MAP kinases; citrullination of histone; transcription
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Khan, M.A.; Pace-Asciak, C.; Al-Hassan, J.M.; Afzal, M.; Liu, Y.F.; Oommen, S.; Paul, B.M.; Nair, D.; Palaniyar, N. Furanoid F-Acid F6 Uniquely Induces NETosis Compared to C16 and C18 Fatty Acids in Human Neutrophils. Biomolecules 2018, 8, 144.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Biomolecules EISSN 2218-273X Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top