Bioactive Ether Lipids: Primordial Modulators of Cellular Signaling

Rangholia, Nikhil; Leisner, Tina M.; Holly, Stephen P.

doi:10.3390/metabo11010041

Cited by 32 publications

(21 citation statements)

References 125 publications

(84 reference statements)

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“…Choline kinase, an enzyme essential for PC biosynthesis, is activated in RA synovial fibroblasts, thereby promoting cell migration and resistance to apoptosis 49 . Ether-linked lipids are synthesized by inflammatory stimuli and incorporated into the cellular membrane, where they act as cellular signaling molecules and antioxidants 50 , 51 . SM is involved in various pathophysiological functions, including apoptosis, autophagy, proliferation, differentiation, and invasiveness 37 .…”

Section: Discussionmentioning

confidence: 99%

Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis

et al. 2022

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Lipid mediators are crucial for the pathogenesis of rheumatoid arthritis (RA); however, global analyses have not been undertaken to systematically define the lipidome underlying the dynamics of disease evolution, activation, and resolution. Here, we performed untargeted lipidomics analysis of synovial fluid and serum from RA patients at different disease activities and clinical phases (preclinical phase to active phase to sustained remission). We found that the lipidome profile in RA joint fluid was severely perturbed and that this correlated with the extent of inflammation and severity of synovitis on ultrasonography. The serum lipidome profile of active RA, albeit less prominent than the synovial lipidome, was also distinguishable from that of RA in the sustained remission phase and from that of noninflammatory osteoarthritis. Of note, the serum lipidome profile at the preclinical phase of RA closely mimicked that of active RA. Specifically, alterations in a set of lysophosphatidylcholine, phosphatidylcholine, ether-linked phosphatidylethanolamine, and sphingomyelin subclasses correlated with RA activity, reflecting treatment responses to anti-rheumatic drugs when monitored serially. Collectively, these results suggest that analysis of lipidome profiles is useful for identifying biomarker candidates that predict the evolution of preclinical to definitive RA and could facilitate the assessment of disease activity and treatment outcomes.

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Section: Discussionmentioning

confidence: 99%

Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis

et al. 2022

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“…The biosynthesis of plasmalogens starts in the subcellular organelle peroxisome and completed in the endoplasmic reticulum (ER) ( Rangholia et al, 2021 ). Plasmalogen deficiency has been reported to be associated with several human diseases as well as aging ( Bozelli et al, 2021 ; Pham et al, 2021 ).…”

Section: Significance Of Plasmalogens As Bioactive Vinyl-ether Lipidsmentioning

confidence: 99%

Plasmalogenic Lipid Analogs as Platelet-Activating Factor Antagonists: A Potential Novel Class of Anti-inflammatory Compounds

Rong

Wang

Angelova

et al. 2022

Front. Cell Dev. Biol.

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Plasmalogens and Platelet-Activating Factor (PAF) are both bioactive ether phospholipids. Whereas plasmalogens are recognized for their important antioxidant function and modulatory role in cell membrane structure and dynamics, PAF is a potent pro-inflammatory lipid mediator known to have messenger functions in cell signaling and inflammatory response. The relationship between these two types of lipids has been rarely studied in terms of their metabolic interconversion and reciprocal modulation of the pro-inflammation/anti-inflammation balance. The vinyl-ether bonded plasmalogen lipid can be can be the lipid sources for the precursor of the biosynthesis of ether-bonded PAF. In this opinion paper, we suggest a potential role of plasmalogenic analogs of PAF as modulators and PAF antagonists (anti-PAF). We discuss that the metabolic interconversion of these two lipid kinds may be explored towards the development of efficient preventive and relief strategies against PAF-mediated pro-inflammation. We propose that plasmalogen analogs, acting as anti-PAF, may be considered as a new class of bioactive anti-inflammatory drugs. Despite of the scarcity of available experimental data, the competition between PAF and its natural plasmalogenic analogs for binding to the PAF receptor (PAF-R) can be proposed as a mechanistic model and potential therapeutic perspective against multiple inflammatory diseases (e.g., cardiovascular and neurodegenerative disorders, diabetes, cancers, and various manifestations in coronavirus infections such as COVID-19).

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“…Ether lipids have been considered to be involved in the formation of macro-and microdomains, which are required for the compartmentalization of highly polarized sperm membrane [123]. In addition, since ether linkages are not readily cleaved by lipase action, ether lipids may maintain stability of sperm membrane [124,125].…”

Section: Ether Lipidsmentioning

confidence: 99%

Sperm Lipid Markers of Male Fertility in Mammals

Shan

Hirschfeld

et al. 2021

IJMS

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Sperm plasma membrane lipids are essential for the function and integrity of mammalian spermatozoa. Various lipid types are involved in each key step within the fertilization process in their own yet coordinated way. The balance between lipid metabolism is tightly regulated to ensure physiological cellular processes, especially referring to crucial steps such as sperm motility, capacitation, acrosome reaction or fusion. At the same time, it has been shown that male reproductive function depends on the homeostasis of sperm lipids. Here, we review the effects of phospholipid, neutral lipid and glycolipid homeostasis on sperm fertilization function and male fertility in mammals.

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Bioactive Ether Lipids: Primordial Modulators of Cellular Signaling

Cited by 32 publications

References 125 publications

Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis

Lipidome profile predictive of disease evolution and activity in rheumatoid arthritis

Plasmalogenic Lipid Analogs as Platelet-Activating Factor Antagonists: A Potential Novel Class of Anti-inflammatory Compounds

Sperm Lipid Markers of Male Fertility in Mammals

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