Protein Lipoxidation: Basic Concepts and Emerging Roles

Abstract

Protein lipoxidation is a non-enzymatic post-translational modification that consists of the covalent addition of reactive lipid species to proteins. This occurs under basal conditions but increases in situations associated with oxidative stress. Protein targets for lipoxidation include metabolic and signalling enzymes, cytoskeletal proteins, and transcription factors, among others. There is strong evidence for the involvement of protein lipoxidation in disease, including atherosclerosis, neurodegeneration, and cancer. Nevertheless, the involvement of lipoxidation in cellular regulatory mechanisms is less understood. Here we review basic aspects of protein lipoxidation and discuss several features that could support its role in cell signalling, including its selectivity, reversibility, and possibilities for regulation at the levels of the generation and/or detoxification of reactive lipids. Moreover, given the great structural variety of electrophilic lipid species, protein lipoxidation can contribute to the generation of multiple structurally and functionally diverse protein species. Finally, the nature of the lipoxidised proteins and residues provides a frameshift for a complex interplay with other post-translational modifications, including redox and redox-regulated modifications, such as oxidative modifications and phosphorylation, thus strengthening the importance of detailed knowledge of this process.

Protective effects of cannabidiol on the membrane proteins of skin keratinocytes exposed to hydrogen peroxide via participation in the proteostasis network

“…However, it is known, that dual oxidase 1 deficiency can also induce the release of pro-inflammatory cytokines such as IFNγ and TNFα [ 91 ]. The above suggestions are confirmed by studies of other authors, which have shown that the formation of 4-ONE-protein adducts is associated with the inhibition of pyruvate kinase and hsp90 [ 69 ] and high-density lipoproteins dysfunction [ 24 ]. However, since the formation of adducts promotes the inhibition of the activity of these enzymes, the use of CBD may protect keratinocytes from the oxidative stress and inflammation associated with H 2 O 2 action.…”

“…This may significantly improve the efficiency of their proteolytic degradation and, consequently, prevent pathological accumulation in keratinocytes. Despite the lack of direct data on the effect of 60 kDa chaperonin on MDA-protein adducts formation, it is known that 4-HNE/4-ONE modifications can lead to loss of activity of the chaperone proteins Hsp70 and Hsp90 [ 69 ]. Thus, a reduction in MDA-protein adduct formation may suggest a protective effect of CBD against the 60 kDa chaperonin.…”

Cellular Response against Oxidative Stress, a Novel Insight into Lupus Nephritis Pathogenesis

“…In SLE, oxidative stress is involved in the formation of advanced glycation end products (AGEs) and advanced lipoperoxidation end products (ALEs), compounds with proinflammatory characteristics. AGEs and ALEs synthesis is realized through condensation reactions between electrophile and nucleophile reactants [ 17 , 21 , 22 , 23 , 24 , 25 ]. AGEs and ALEs are immunogen and they determine antibodies synthesis.…”

Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol

“…Previous studies have demonstrated that liver pathologies such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic hepatitis (NASH), contribute to lipid disorders commonly terms as dyslipidemia [ 4 ]. Phospholipids containing polyunsaturated fatty acids (PUFAs) are particularly susceptible to the action of reactive oxygen species (ROS), which promote peroxidation based on the classic chain reaction mechanism, resulting in the generation of low-molecular-weight, reactive α,β-unsaturated aldehydes and/or cyclic derivatives such as isoprostanes or neuroprostanes depending on the type of oxidation of the PUFAs underwent [ 5 , 6 ]. Phospholipid oxidation also takes place under the influence of lipolytic enzymes such as: phospholipases, lipoxygenases and cyclooxygenases, which activities are enhanced during oxidative conditions.…”