The nucleus has been identified as the subcellular site to which many arachidonate-metabolizing enzymes are associated following cell activation. However, little is known about the subcellular distribution of arachidonate (AA) itself nor about the location of the central enzyme involved in AA-phospholipid remodeling, CoA-independent transacylase (CoA-IT). Nuclei from human monocyte-like THF-1 cells were isolated and the AA content of phospholipid (PL) subclasses was measured by negative ion chemical ionization GC/MS. Approximately 25% of the cellular AA in THP-1 cells was associated with the nucleus. Pronounced differences were observed in AA-containing phospholipid subclasses of nuclear and non-nuclear membranes.; cell nuclei were enriched in AA-containing 1-acyl-linked PL species whereas other cellular membranes were more enriched in AA-containing PL possessing 1-ether linkages. While whole cells readily remodeled labeled AA from 1-acyl-to 1-ether-linked phospholipids, isolated nuclei were not able to remodel AA incorporated into nuclear membrane PL. Isolated nuclei contained approximately 40% of the total cellular CoA-IT activity. Together, these data reveal that nuclei contain the major donor substrates for the CoA-IT reaction as well as some CoA-IT activity while non-nuclear membranes contain predominantly acceptor substrates for the CoA-IT reaction and some CoA-IT activity. Hence the CoA-IT reaction may be responsible for not only maintaining the distribution of AA among PL subclasses but also for regulating the movement of AA between subcellular locations.
|Original language||English (US)|
|State||Published - 1997|
ASJC Scopus subject areas
- Molecular Biology