Lysophospholipid acyltransferases: novel potential regulators of the inflammatory response and target for new drug discovery.
Molecular and biochemical analyses of membrane phospholipids have revealed that, in addition to their physico-chemical properties, the metabolites of phospholipids play a crucial role in the recognition, signalling and responses of cells to a variety of stimuli. Such responses are mediated in large part by the removal and/or addition of different acyl chains to provide different phospholipid molecular species. The reacylation reactions, catalysed by specific acyltransferases control phospholipid composition and the availability of the important mediators free arachidonic acid and lysophospholipids. Lysophospholipid acyltransferases are therefore key control points for cellular responses to a variety of stimuli including inflammation. Regulation or manipulation of lysophospholipid acyltransferases may thus provide important mechanisms for novel anti-inflammatory therapies. This review will highlight mammalian lysophospholipid acyltransferases with particular reference to the potential role of lysophosphatidylcholine acyltransferase and its substrates in sepsis and other inflammatory conditions and as a potential target for novel anti-inflammatory therapies.
Centre for Research in Biomedicine, Faculty of Health and Life Sciences, Frenchay Campus, University of the West of England, Bristol, UK. simon.jackson@uwe.ac.uk
Simon K
SK
Jackson
Wondwossen
W
Abate
Amanda J
AJ
Tonks
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000037:antagonists & inhibitors / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001930:Brain Injuries / Q000378:metabolism; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000209:etiology*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D007371:Interferon-gamma; D008243:1-Acylglycerophosphocholine O-Acyltransferase