Related Experiment Video

Updated: Aug 23, 2026

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
13:38

Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells

Published on: January 18, 2017

Oxidized omega-3 fatty acids inhibit NF-kappaB activation via a PPARalpha-dependent pathway

Archana Mishra1, Ashok Chaudhary, Sanjeev Sethi

  • 1Department of Pathology, 5243 RCP, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|July 3, 2004
PubMed
Abstract

Insights

Oxidized omega-3 fatty acids, unlike native forms, inhibit inflammatory chemokines by blocking nuclear factor-kappaB (NF-kappaB) activation through a peroxisome proliferator-activated receptor alpha (PPARalpha)-dependent pathway.

Area of Science:

  • Biochemistry
  • Immunology
  • Molecular Biology

Background:

  • Omega-3 fatty acids are known for their anti-inflammatory properties.
  • The specific effects of oxidized versus native omega-3s on endothelial chemokine expression are not fully understood.

Purpose of the Study:

  • To investigate the impact of oxidized and native omega-3 fatty acids on endothelial chemokines.
  • To elucidate the mechanism by which oxidized omega-3s inhibit chemokine expression.

Main Methods:

  • Enzyme-linked immunosorbent assays (ELISAs) were used to measure chemokine levels.
  • Electrophoretic mobility shift assays (EMSAs) assessed nuclear factor-kappaB (NF-kappaB) activation.
  • Western blot analysis examined protein phosphorylation and ubiquitination.

Main Results:

  • Oxidized EPA and DHA significantly inhibited monocyte chemoattractant protein (MCP)-1 and IL-8 expression.
  • Oxidized EPA potently inhibited cytokine-induced NF-kappaB activation.
  • Inhibition of NF-kappaB by oxidized EPA was dependent on peroxisome proliferator-activated receptor alpha (PPARalpha).

Conclusions:

  • Oxidized omega-3 fatty acids exhibit anti-inflammatory effects by inhibiting NF-kappaB activation.
  • The mechanism involves a PPARalpha-dependent pathway.
  • These findings suggest oxidized omega-3s contribute to the anti-inflammatory benefits of fish oil.

Related Concept Videos

NF-κB-dependent Signaling Pathway02:26

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...