Novel bioactive glycerol-based lysophospholipids: New data – New insight into their function

Published Date
April 2013, Vol.95(4):667–679, doi:10.1016/j.biochi.2012.10.009

Review

Author 

Anna Grzelczyk

Edyta Gendaszewska-Darmach ^,

Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland

Received 6 May 2012. Accepted 11 October 2012. Available online 22 October 2012. 

Abstract

Based on the results of research conducted over last two decades, lysophospholipids (LPLs) were observed to be not only structural components of cellular membranes but also biologically active molecules influencing a broad variety of processes such as carcinogenesis, neurogenesis, immunity, vascular development or regulation of metabolic diseases. With a growing interest in the involvement of extracellular lysophospholipids in both normal physiology and pathology, it has become evident that those small molecules may have therapeutic potential. While lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) have been studied in detail, other LPLs such as lysophosphatidylglycerol (LPG), lysophosphatidylserine (LPS), lysophosphatidylinositol (LPI), lysophosphatidylethanolamine (LPE) or even lysophosphatidylcholine (LPC) have not been elucidated to such a high degree. Although information concerning the latter LPLs is sparse as compared to LPA and S1P, within the last couple of years much progress has been made. Recently published data suggest that these compounds may regulate fundamental cellular activities by modulating multiple molecular targets, e.g. by binding to specific receptors and/or altering the structure and fluidity of lipid rafts. Therefore, the present review is devoted to novel bioactive glycerol-based lysophospholipids and recent findings concerning their functions and possible signaling pathways regulating physiological and pathological processes.

Graphical abstract

Multiple activities of bioactive lysophospholipids. LPLs act mainly through direct interaction with a specific GPCR or/and ion channel or through modulation of lipid rafts organization. Incorporation of LPLs into the cell membrane also leads to dimerisation/oligomerisation of receptors and triggering downstream signaling pathways. Besides, micelles composed of LPLs are able to disrupt cell membrane integrity and lysis of whole cells.

Highlights

► The review is devoted to novel bioactive lysophospholipids: LPI, LPE, LPS, LPG, LPC. ► We summarize their in vivo distribution and biosynthesis pathways. ► Those LPLs regulate fundamental cellular functions by modulating multiple targets. ► They alter the structure and fluidity of lipid rafts. ► We comprehend the progress in deorphanizing GPCRs for LPC, LPS, LPI, LPG and LPE.

Keywords

• Lysophospholipids
• G-protein coupled receptors
• Membranes/fluidity
• Phospholipases

Abbreviations

• ALP, alkaline phosphatase
• CMC, critical micelle concentration
• FPRL1, formyl peptide receptor like-1
• HODE, hydroxyoctadecadienoic acid
• IAP, intestinal alkaline phosphatase
• LPA, lysophosphatidic acid
• LPC, lysophosphatidylcholine
• LPE, lysophosphatidylethanolamine
• LPG, lysophosphatidylglycerol
• LPI, lysophosphatidylinositol
• LPL, lysophospholipid
• LPS, lysophosphatidylserine
• LPT, lysophosphatidylthreonine
• OEA, oleoylethanolamide
• PC, phosphatidylcholine
• PE, phosphatidylethanolamine
• PL, phospholipid
• PLC, phospholipase C
• PS, phosphatidylserine
• ROS, reactive oxygen species
• S1P, sphingosine-1-phosphate
• SPC, sphingosylphosphorylcholine
• TRP, transient receptor potential

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Fig. 1.

 Table 1

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 Table 2

Table 2.

 Table 3

Table 3.

Fig. 2.

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