Inflammation, lipid (per)oxidation and redox regulation

Abstract

Significance: Inflammation increases during the aging process. It is linked to mitochondrial dysfunction and increased reactive oxygen species (ROS) production. Mitochondrial macromolecules are critical targets of oxidative damage; they contribute to respiratory uncoupling with increased ROS production, redox stress, and a cycle of senescence, cytokine production, and impaired oxidative phosphorylation. Targeting the formation or accumulation of oxidized biomolecules, particularly oxidized lipids, in immune cells and mitochondria could be beneficial for age-related inflammation and comorbidities. Recent Advances: Inflammation is central to age-related decline in health and exhibits a complex relationship with mitochondrial redox state and metabolic function. Improvements in mass spectrometric methods have led to the identification of families of oxidized phospholipids (OxPLs), cholesterols, and fatty acids that increase during inflammation and which modulate nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPARγ), activator protein 1 (AP1), and NF-κB redox-sensitive transcription factor activity. Critical Issues: The kinetic and spatial resolution of the modified lipidome has profound and sometimes opposing effects on inflammation, promoting initiation at high concentration and resolution at low concentration of OxPLs. Future Directions: There is an emerging opportunity to prevent or delay age-related inflammation and vascular comorbidity through a resolving (oxy)lipidome that is dependent on improving mitochondrial quality control and restoring redox homeostasis.

Publication DOI: https://doi.org/10.1089/ars.2020.8022
Divisions: Aston Medical School
Life & Health Sciences
Life & Health Sciences > Biosciences
Life & Health Sciences > Chronic and Communicable Conditions
Life & Health Sciences > Cellular and Molecular Biomedicine
Additional Information: The final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/ars.2020.8022
Full Text Link:
Related URLs: https://www.lie ... 9/ars.2020.8022 (Publisher URL)
PURE Output Type: Article
Published Date: 2020-07-20
Published Online Date: 2020-01-28
Accepted Date: 2020-01-01
Authors: Dias, Irundika ( 0000-0002-6620-8221)
Milic, Ivana ( 0000-0001-7531-7561)
Heiss, Christian
Ademowo, Opeyemi Stella
Polidori, M Cristina
Devitt, Andrew ( 0000-0002-4651-6761)
Griffiths, H R

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Version: Accepted Version

Access Restriction: Restricted to Repository staff only until 28 January 2021.


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