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Brain Research Bulletin Mar 2023Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. Synthesis of plasmalogens is initiated in peroxisomes and completed in... (Review)
Review
Plasmalogens are a unique family of cellular glycerophospholipids that contain a vinyl-ether bond. Synthesis of plasmalogens is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of patients with deficiency in peroxisome biogenesis suggests that de novo synthesis of plasmalogens contributes significantly to plasmalogen homeostasis in humans. Plasmalogen biosynthesis is spatiotemporally regulated by a feedback mechanism that senses the amount of plasmalogens in the inner leaflet of the plasma membrane and regulates the stability of fatty acyl-CoA reductase 1 (FAR1), the rate-limiting enzyme for plasmalogen biosynthesis. Dysregulation of plasmalogen synthesis impairs cholesterol synthesis in cells and brain, resulting in the reduced expression of genes such as mRNA encoding myelin basic protein, a phenotype found in the cerebellum of plasmalogen-deficient mice. In this review, we summarize the current knowledge of molecular mechanisms underlying the regulation of plasmalogen biosynthesis and the link between plasmalogen homeostasis and cholesterol biosynthesis, and address the pathogenesis of impaired plasmalogen homeostasis in rodent and humans.
Topics: Humans; Animals; Mice; Plasmalogens; Homeostasis; Cholesterol; Mammals
PubMed: 36720320
DOI: 10.1016/j.brainresbull.2023.01.011 -
Brain Research Bulletin Oct 2022Ether phospholipid compositions are altered in the plasma or brain of patients with brain disorders, such as Alzheimer and Parkinson's disease, including those with... (Review)
Review
Ether phospholipid compositions are altered in the plasma or brain of patients with brain disorders, such as Alzheimer and Parkinson's disease, including those with psychiatric disorders like schizophrenia and bipolar disorders. Notably, plasmenyl ethanolamine has a unique chemical structure, i.e., a vinyl-ether bond at the sn-1 position, which mainly links with polyunsaturated fatty acids (PUFAs) at the sn-2 position. Those characteristic moieties give plasmalogen molecules unique biophysical and chemical properties that modulate membrane trafficking, lipid rafts, intramolecular PUFA moieties, and oxidative states. Previous reports suggested that a deficiency in plasmenyl ethanolamine leads to disturbances of the myelin structure, synaptic neurotransmission and intracellular signaling, apoptosis of neurons, and neuroinflammation, accompanied by cognitive disturbances and aberrant behaviors like hyperactivity in mice. Therefore, this review summarizes the relationship between the biological functions of plasmalogen. We also proposed biophysical properties that alter brain phospholipid compositions related to aberrant behaviors and cognitive dysfunction. Finally, a brief review of possible remedial plasmalogen replacement therapies for neurological, psychiatric, and developmental disorders attributable to disturbed plasmalogen compositions in the organs and cells was conducted.
Topics: Animals; Brain; Cognition; Ethanolamines; Humans; Mice; Oxidation-Reduction; Plasmalogens
PubMed: 35970332
DOI: 10.1016/j.brainresbull.2022.08.008 -
Brain Research Bulletin Feb 2023On the basis of findings that cultured rat hepatocytes secrete lipoprotein with a high plasmalogen content and the occurrence of this lipid in human serum, it has been... (Review)
Review
On the basis of findings that cultured rat hepatocytes secrete lipoprotein with a high plasmalogen content and the occurrence of this lipid in human serum, it has been suggested that hepatocytes play a role in the supply of plasmalogens to tissues. We tested this hypothesis in a mouse with a hepatocyte-specific defect in peroxisomes, an organelle essentially required for plasmalogen biosynthesis. We analyzed plasmalogens in lipid extracts of forebrain, liver and five further tissues and in plasma by reaction with dansylhydrazine in hydrochloric acid, which cleaves the vinyl ether of plasmalogens and forms a fluorescent dansylhydrazone, which we quantified by reversed phase high performance liquid chromatography. Reaction with dansylhydrazine in acetic acid was used to quantify free aldehydes as a control. Our results show normal levels of plasmalogens in plasma and in all tissues examined, including forebrain and the liver, irrespective of the inactivation of hepatic peroxisomes. None of the selected ether lipids analyzed by mass spectrometry in plasma and liver was decreased in the mice deficient in liver peroxisomes. In contrast, we found three plasmenylcholine species which were even significantly increased in the livers of these animals. Quantification of mRNA expression of plasmalogen biosynthetic enzymes revealed particularly low expression of fatty acyl-CoA reductase, the key regulatory enzyme of plasmalogen biosynthesis, in liver, with and without hepatic peroxisome deficiency. Our results do not support the suggested role of hepatocytes in supplying plasmalogens to tissues.
Topics: Animals; Mice; Dansyl Compounds; Hepatocytes; Peroxisome-Targeting Signal 1 Receptor; Plasmalogens
PubMed: 36584717
DOI: 10.1016/j.brainresbull.2022.12.007 -
FEBS Letters Sep 2017Plasmalogens, mostly ethanolamine-containing alkenyl ether phospholipids, are a major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes... (Review)
Review
Plasmalogens, mostly ethanolamine-containing alkenyl ether phospholipids, are a major subclass of glycerophospholipids. Plasmalogen synthesis is initiated in peroxisomes and completed in the endoplasmic reticulum. The absence of plasmalogens in several organs of peroxisome biogenesis-defective patients suggests that the de novo synthesis of plasmalogens plays a pivotal role in its homeostasis in tissues. Plasmalogen synthesis is regulated by modulating the stability of fatty acyl-CoA reductase 1 on peroxisomal membranes, a rate-limiting enzyme in plasmalogen synthesis, by sensing plasmalogens in the inner leaflet of plasma membranes. Dysregulation of plasmalogen homeostasis impairs cholesterol biosynthesis by altering the stability of squalene monooxygenase, a key enzyme in cholesterol biosynthesis, implying physiological consequences of plasmalogen homeostasis with respect to cholesterol metabolism in cells, as well as in organs such as the liver.
Topics: Animals; Cell Membrane; Homeostasis; Humans; Mammals; Peroxisomes; Plasmalogens
PubMed: 28686302
DOI: 10.1002/1873-3468.12743 -
Lipids in Health and Disease Mar 2018The plasmalogens are a class of glycerophospholipids which contain a vinyl-ether and an ester bond at the sn-1 and sn-2 positions, respectively, in the glycerol... (Review)
Review
The plasmalogens are a class of glycerophospholipids which contain a vinyl-ether and an ester bond at the sn-1 and sn-2 positions, respectively, in the glycerol backbone. They constitute 10 mol% of the total mass of phospholipids in humans, mainly as membrane structure components. Plasmalogens are important for the organization and stability of lipid raft microdomains and cholesterol-rich membrane regions involved in cellular signaling. In addition to their structural roles, a subset of ether lipids are thought to function as endogenous antioxidants and emerging studies suggest that they are involved in cell differentiation and signaling pathways. Although the clinical significance of plasmalogens is linked to peroxisomal disorders, the pathophysiological roles and their possible metabolic pathways are not fully understood since they present unique structural attributes for the different tissue types. Studies suggest that changes in plasmalogen metabolism may contribute to the development of various types of cancer. Here, we review the molecular characteristics of plasmalogens in order to significantly increase our understanding of the plasmalogen molecule and its involvement in gastrointestinal cancers as well as other types of cancers.
Topics: Antineoplastic Agents; Biomarkers, Tumor; Gastrointestinal Neoplasms; Humans; Lipid Metabolism; Phospholipid Ethers; Plasmalogens
PubMed: 29514688
DOI: 10.1186/s12944-018-0685-9 -
Brain Research Bulletin Aug 2022Microglia plays an important role in the production of inflammation in the central nervous system. Excessive nerve inflammation can cause neuronal damage and... (Review)
Review
Microglia plays an important role in the production of inflammation in the central nervous system. Excessive nerve inflammation can cause neuronal damage and neurodegenerative disease. It has been shown that EPA-enriched ethanolamine plasmalogen (EPA-PlsEtn) significantly inhibited the expressions of inflammatory factors and suppressed neuronal loss in a rat model of Alzheimer's disease. However, whether EPA-PlsEtn protects against neuronal loss by inhibiting the activation of microglia is still not clear. Therefore, we examined the effect of PlsEtn on SH-SY5Y cells incubated by conditioned medium from LPS-induced BV2 cells as a neuroinflammation model. Results showed that pre-incubation of LPS-induced BV2 cells with PlsEtn significantly improved the viability of SH-SY5Y cells by reducing the early apoptosis. The increasing production of NO and TNF-α in BV2 cells was reversed by PlsEtn treatment, while the decreasing level of IL-10 was raised. Polarization toward M1 phenotype and activation of NLRP3 inflammasome pathways are attenuated significantly by pre-treatment of PlsEtn in LPS-induced BV2 cells. The study provides evidence for a positive effect of PlsEtn on neuroprotection and the inhibition of neuroinflammation, and PlsEtn may be explored as a potential functional ingredient with neuroprotection effects.
Topics: Animals; Cell Line; Humans; Inflammation; Lipopolysaccharides; Microglia; Neuroblastoma; Neurodegenerative Diseases; Plasmalogens; Rats
PubMed: 35728742
DOI: 10.1016/j.brainresbull.2022.06.002 -
Biochimica Et Biophysica Acta.... Jul 2020Long-chain fatty aldehydes are present in low concentrations in mammalian cells and serve as intermediates in the interconversion between fatty acids and fatty alcohols.... (Review)
Review
Long-chain fatty aldehydes are present in low concentrations in mammalian cells and serve as intermediates in the interconversion between fatty acids and fatty alcohols. The long-chain fatty aldehydes are generated by enzymatic hydrolysis of 1-alkyl-, and 1-alkenyl-glycerophospholipids by alkylglycerol monooxygenase, plasmalogenase or lysoplasmalogenase while hydrolysis of sphingosine-1-phosphate (S1P) by S1P lyase generates trans ∆2-hexadecenal (∆2-HDE). Additionally, 2-chloro-, and 2-bromo- fatty aldehydes are produced from plasmalogens or lysoplasmalogens by hypochlorous, and hypobromous acid generated by activated neutrophils and eosinophils, respectively while 2-iodofatty aldehydes are produced by excess iodine in thyroid glands. The 2-halofatty aldehydes and ∆2-HDE activated JNK signaling, BAX, cytoskeletal reorganization and apoptosis in mammalian cells. Further, 2-chloro- and 2-bromo-fatty aldehydes formed GSH and protein adducts while ∆2-HDE formed adducts with GSH, deoxyguanosine in DNA and proteins such as HDAC1 in vitro. ∆2-HDE also modulated HDAC activity and stimulated H3 and H4 histone acetylation in vitro with lung epithelial cell nuclear preparations. The α-halo fatty aldehydes elicited endothelial dysfunction, cellular toxicity and tissue damage. Taken together, these investigations suggest a new role for long-chain fatty aldehydes as signaling lipids, ability to form adducts with GSH, proteins such as HDACs and regulate cellular functions.
Topics: Aldehyde-Lyases; Aldehydes; Animals; Histone Deacetylases; Humans; Plasmalogens; Signal Transduction
PubMed: 32171908
DOI: 10.1016/j.bbalip.2020.158681 -
Progress in Lipid Research Jul 2023Plasmalogen is a major phospholipid of mammalian cell membranes. Recently it is becoming evident that the sn-1 vinyl-ether linkage in plasmalogen, contrasting to the... (Review)
Review
Plasmalogen is a major phospholipid of mammalian cell membranes. Recently it is becoming evident that the sn-1 vinyl-ether linkage in plasmalogen, contrasting to the ester linkage in the counterpart diacyl glycerophospholipid, yields differential molecular characteristics for these lipids especially related to hydrocarbon-chain order, so as to concertedly regulate biological membrane processes. A role played by NMR in gaining information in this respect, ranging from molecular to tissue levels, draws particular attention. We note here that a broad range of enzymes in de novo synthesis pathway of plasmalogen commonly constitute that of diacyl glycerophospholipid. This fact forms the basis for systematic crosstalk that not only controls a quantitative balance between these lipids, but also senses a defect causing loss of lipid in either pathway for compensation by increase of the counterpart lipid. However, this inherent counterbalancing mechanism paradoxically amplifies imbalance in differential effects of these lipids in a diseased state on membrane processes. While sharing of enzymes has been recognized, it is now possible to overview the crosstalk with growing information for specific enzymes involved. The overview provides a fundamental clue to consider cell and tissue type-dependent schemes in regulating membrane processes by plasmalogen and diacyl glycerophospholipid in health and disease.
Topics: Animals; Plasmalogens; Cell Membrane; Mammals
PubMed: 37169310
DOI: 10.1016/j.plipres.2023.101234 -
Life Science Alliance Aug 2019Lipid homeostasis is crucial in human health. Barth syndrome (BTHS), a life-threatening disease typically diagnosed with cardiomyopathy and neutropenia, is caused by...
Lipid homeostasis is crucial in human health. Barth syndrome (BTHS), a life-threatening disease typically diagnosed with cardiomyopathy and neutropenia, is caused by mutations in the mitochondrial transacylase tafazzin. By high-resolution P nuclear magnetic resonance (NMR) with cryoprobe technology, recently we found a dramatic loss of choline plasmalogen in the tafazzin-knockdown (TAZ-KD) mouse heart, besides observing characteristic cardiolipin (CL) alterations in BTHS. In inner mitochondrial membrane where tafazzin locates, CL and diacyl phosphatidylethanolamine are known to be essential via lipid-protein interactions reflecting their cone shape for integrity of respiratory chain supercomplexes and cristae ultrastructure. Here, we investigate the TAZ-KD brain, liver, kidney, and lymphoblast from patients compared with controls. We identified common yet markedly cell type-dependent losses of ethanolamine plasmalogen as the dominant plasmalogen class therein. Tafazzin function thus critically relates to homeostasis of plasmalogen, which in the ethanolamine class has conceivably analogous and more potent molecular functions in mitochondria than diacyl phosphatidylethanolamine. The present discussion of a loss of plasmalogen-protein interaction applies to other diseases with mitochondrial plasmalogen loss and aberrant forms of this organelle, including Alzheimer's disease.
Topics: Acyltransferases; Animals; Barth Syndrome; Cardiolipins; Cardiomyopathies; Female; Humans; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria; Mitochondrial Membranes; Plasmalogens; Transcription Factors
PubMed: 31434794
DOI: 10.26508/lsa.201900348 -
Journal of Biochemistry Nov 2019Ether glycerolipids, plasmalogens are found in various mammalian cells and tissues. However, physiological role of plasmalogens in epithelial cells remains unknown. We...
Ether glycerolipids, plasmalogens are found in various mammalian cells and tissues. However, physiological role of plasmalogens in epithelial cells remains unknown. We herein show that synthesis of ethanolamine-containing plasmalogens, plasmenylethanolamine (PlsEtn), is deficient in MCF7 cells, an epithelial cell line, with severely reduced expression of alkyl-dihydroxyacetonephosphate synthase (ADAPS), the second enzyme in the PlsEtn biosynthesis. Moreover, expression of ADAPS or supplementation of PlsEtn containing C18-alkenyl residue delays the migration of MCF7 cells as compared to that mock-treated MCF7 and C16-alkenyl-PlsEtn-supplemented MCF7 cells. Localization of E-cadherin to cell-cell junctions is highly augmented in cells containing C18-alkenyl-PlsEtn. Together, these results suggest that PlsEtn containing C18-alkenyl residue plays a distinct role in the integrity of E-cadherin-mediated adherens junction.
Topics: Adherens Junctions; Humans; MCF-7 Cells; Plasmalogens; Tumor Cells, Cultured
PubMed: 31236591
DOI: 10.1093/jb/mvz049