The Lysophosphatidylserines—An Emerging Class of Signalling Lysophospholipids

Shanbhag, Karthik; Mhetre, Amol; Khandelwal, Neha; Kamat, Siddhesh S.

doi:10.1007/s00232-020-00133-2

Cited by 25 publications

(41 citation statements)

References 153 publications

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“…More recently Cravatt's group identified α/β-hydrolase domain-containing protein 16 A (ABHD16A) as a candidate of an intracellular LysoPS producing enzyme, and ABHD12 and ABHD6 as LysoPS degrading enzymes [13,19,25]. Since the enzymatic characteristics, biological and pathological roles of these enzymes have been elegantly described in [26], we briefly mention their properties.…”

Section: Synthetic and Degradative Pathways Of Lysopsmentioning

confidence: 99%

Current Knowledge on the Biology of Lysophosphatidylserine as an Emerging Bioactive Lipid

Omi

Kano

Aoki

2021

Cell Biochem Biophys

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Lysophosphatidylserine (LysoPS) is an emerging lysophospholipid (LPL) mediator, which acts through G protein-coupled receptors, like lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P). LysoPS is detected in various tissues and cells and thought to be produced mainly by the deacylation of phosphatidylserine. LysoPS has been known to stimulate degranulation of mast cells. Recently, four LysoPS-specific G protein-coupled receptors (GPCRs) were identified. These GPCRs belong to the P2Y family which covers receptors for nucleotides and LPLs and are predominantly expressed in immune cells such as lymphocytes and macrophages. Studies on knockout mice of these GPCRs have revealed that LysoPS has immune-modulatory functions. Up-regulation of a LysoPS-producing enzyme, PS-specific phospholipase A1, was frequently observed in situations where the immune system is activated including autoimmune diseases and organ transplantations. Therefore, modulation of LysoPS signaling appears to be a promising method for providing therapies for the treatment of immune diseases. In this review, we summarize the biology of LysoPS-producing enzymes and receptors, recent developments in LysoPS signal modulators, and prospects for future therapeutic applications.

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Section: Synthetic and Degradative Pathways Of Lysopsmentioning

confidence: 99%

Current Knowledge on the Biology of Lysophosphatidylserine as an Emerging Bioactive Lipid

Omi

Kano

Aoki

2021

Cell Biochem Biophys

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“…have confirmed the activity of PS vesicle also on the monocytic leukemia cell lines THP‐1 but no effects were observed for phosphoserine or GPS. By contrast, in recent years lyso‐PS have emerged as signaling molecules in several biological processes, and deregulation of their metabolism has been linked to various human pathophysiological conditions [52] . Lyso‐PS are involved in the release of histamine from Mast cells, macrophage‐mediated efferocytosis, and inhibition of lymphocytes proliferation.…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, lyso‐PS stimulate intracellular calcium signaling and promote chemotactic migration in human cancer cells. Finally, lyso‐PS have hormone‐like signaling properties facilitating the transport and adsorption of glucose into muscle fibres and adipocytes [52] …”

Section: Introductionmentioning

confidence: 99%

Chemical and Enzymatic Approaches to Esters ofsn‐Glycero‐3‐Phosphoric Acid

et al. 2021

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Esters of sn‐glycero‐3‐phosphoric acid (GPAE) are derivatives of glycerophospholipids in which both the fatty acid chains in sn‐1 and sn‐2 positions are removed. Phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS) are the most abundant glycerophospholipids in Nature. Their deacylated derivatives find application in many industrial sectors; for example, sn‐glycero‐3‐phosphocholine (GPC) is useful as a cognitive enhancer and as a food ingredient, whereas sn‐glycero‐3‐phosphoinositol (GPI) acts as a natural anti‐inflammatory agent. This minireview covers the state‐of‐the‐art of chemical and biocatalytic methods for the obtainment of these lipid‐derived components.

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“…circulating macrophages) signature signaling cues, to initiate its engulfment and clearance from the system via phagocytosis 2,3,[6][7][8] . Amongst the signaling lipids thought to be involved in facilitating phagocytosis 1,2,4 , are the immunomodulatory lysophosphatidylserines (lyso-PSs) 9 and the pro-apoptotic oxidized phosphatidylserines (PSs) 10 .…”

Section: Introductionmentioning

confidence: 99%

The loss of enzymatic activity of the PHARC associated lipase ABHD12 results in increased phagocytosis that causes neuroinflammation

Singh

Kamat

2021

Preprint

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Phagocytosis is an important evolutionary conserved process, essential for clearing pathogens and cellular debris in higher organisms, including humans. This well-orchestrated innate immunological response is intricately regulated by numerous cellular factors, important amongst which, are the immunomodulatory lysophosphatidylserines (lyso-PSs) and the pro-apoptotic oxidized phosphatidylserines (PSs) signaling lipids. Interestingly, in mammals, both these signaling lipids are physiologically regulated by the lipase ABHD12, mutations of which, cause the human neurological disorder PHARC. Despite the biomedical significance of this lipase, detailed mechanistic studies and the specific contribution of ABHD12 to innate processes like phagocytosis remain poorly understood. Here, by immunohistochemical and immunofluorescence approaches, using the murine model of PHARC, we show, that upon an inflammatory stimulus, activated microglial cells in the cerebellum of mice deficient in ABHD12 have an amoeboid morphology, increased soma size, and display heightened phagocytosis activity. We also report that upon an inflammatory stimulus, cerebellar levels of ABHD12 increase to possibly metabolize the heightened oxidized PS levels, temper phagocytosis and in turn control neuroinflammation during oxidative stress. Next, to complement these findings, using biochemical approaches in cultured microglial cells, we show that the pharmacological inhibition and/or genetic deletion of ABHD12 results in increased phagocytic uptake in a fluorescent bead uptake assay. Together, our studies provide compelling evidence that ABHD12 plays an important role in regulating phagocytosis in cerebellar microglial cells, and provides a possible explanation, as to why human PHARC subjects display neuroinflammation and atrophy in the cerebellum.

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The Lysophosphatidylserines—An Emerging Class of Signalling Lysophospholipids

Cited by 25 publications

References 153 publications

Current Knowledge on the Biology of Lysophosphatidylserine as an Emerging Bioactive Lipid

Current Knowledge on the Biology of Lysophosphatidylserine as an Emerging Bioactive Lipid

Chemical and Enzymatic Approaches to Esters ofsn‐Glycero‐3‐Phosphoric Acid

The loss of enzymatic activity of the PHARC associated lipase ABHD12 results in increased phagocytosis that causes neuroinflammation

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