Polyenoic very-long-chain fatty acids mobilise calcium from a thapsigargin-insensitive pool in human neutrophils. The relationship between Ca++ mobilization and superoxide production induced by long- and very-long fatty acids

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dc.contributor.authorHardy, S.
dc.contributor.authorRobinson, B.
dc.contributor.authorFerrante, A.
dc.contributor.authorHii, C.
dc.contributor.authorJohnson, D.
dc.contributor.authorPoulos, A.
dc.contributor.authorMurray, A.
dc.date.issued1995
dc.description.abstractFatty acids with more than 22 carbon atoms (very-long-chain fatty acids; VLCFAs) are normal cellular components that have been implicated in the pathophysiology of a number of peroxisomal disorders. To date, however, essentially nothing is known regarding their biological activities. Ca2+ mobilization is an important intracellular signalling system for a variety of agonists and cell types. Given that several polyunsaturated long-chain fatty acids mobilize intracellular Ca2+ and that we have postulated that the VLCFAs may be involved in signal transduction, we examined whether the tetraenoic VLCFA induced Ca2+ mobilization in human neutrophils. We report that fatty acid-induced intracellular Ca2+ mobilization declined for fatty acid species of more than 20 carbon atoms, but increased again as the carbon chain length approached 30. This Ca2+ mobilization occurred independently of inositol 1,4,5-triphosphate production and protein kinase C translocation and involved both the release of Ca2+ from the intracellular stores and changes to the influx or efflux of the ion. We further observed that triacontatetraenoic acid [30:4(n-6)] mobilized Ca2+ from a thapsigargin-insensitive intracellular pool distinct from the thapsigargin-sensitive pools affected by arachidonic acid [20:4(n - 6)] or N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). 20:4 (n - 6) induced strong superoxide production (chemiluminescence) which was inhibited by thapsigargin pretreatment. In contrast, fatty acid-induced superoxide production progressively declined as the carbon chain length increased beyond 20-22 carbon atoms. Further studies suggested that the thapsigargin-insensitive Ca2+ mobilization elicited by 30:4 (n - 6) was not related to oxyradical formation, while the thapsigargin-sensitive Ca2+ mobilization induced by 20:4 (n - 6) may be involved in the initiation but not necessarily the maintenance of superoxide production. In conclusion, this is the first report to demonstrate a biological activity for the VLCFA and indicates that 30:4 (n - 6) influences second messenger systems in intact cells that differ from those affected by long-chain fatty acids such as 20:4 (n - 6).
dc.description.statementofresponsibilityS J Hardy, B S Robinson, A Ferrante, C S Hii, D W Johnson, A Poulos and A W Murray
dc.identifier.citationBiochemical Journal, 1995; 311(2):689-697
dc.identifier.doi10.1042/bj3110689
dc.identifier.issn0264-6021
dc.identifier.issn1470-8728
dc.identifier.orcidFerrante, A. [0000-0002-2581-6407]
dc.identifier.orcidHii, C. [0000-0002-7107-8935]
dc.identifier.urihttp://hdl.handle.net/2440/7025
dc.language.isoen
dc.publisherPORTLAND PRESS
dc.source.urihttp://www.biochemj.org.proxy.library.adelaide.edu.au/bj/311/bj3110689.htm
dc.subjectNeutrophils
dc.subjectHumans
dc.subjectSuperoxides
dc.subjectCalcium
dc.subjectInositol 1,4,5-Trisphosphate
dc.subjectTerpenes
dc.subjectThapsigargin
dc.subjectFura-2
dc.subjectProtein Kinase C
dc.subjectFatty Acids
dc.subjectOvalbumin
dc.subjectSerum Albumin, Bovine
dc.subjectEnzyme Inhibitors
dc.subjectLuminescent Measurements
dc.subjectSecond Messenger Systems
dc.subjectStructure-Activity Relationship
dc.subjectCalcium-Transporting ATPases
dc.titlePolyenoic very-long-chain fatty acids mobilise calcium from a thapsigargin-insensitive pool in human neutrophils. The relationship between Ca++ mobilization and superoxide production induced by long- and very-long fatty acids
dc.typeJournal article
pubs.publication-statusPublished

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