Selective incorporation of docosahexaenoic acid into lysobisphosphatidic acid in cultured THP‐1 macrophages

Abstract

Lysobisphosphatidic acid (LBPA) is highly accumulated in specific domains of the late endosome and is involved in the biogenesis and function of this organelle. Little is known about the biosynthesis and metabolism of this lipid. We examined its FA composition and the incorporation of exogenous FA into LBPA in the human monocytic leukemia cell line THP-1. The LBPA FA composition in THP-1 cells exhibits an elevated amount of oleic acid (18:1n-9) and enrichment of PUFA, especially DHA (22:6n-3). DHA supplemented to the medium was efficiently incorporated into LBPA. In contrast, arachidonic acid (20:4n-6) was hardly esterified to LBPA under the same experimental conditions. The turnover of DHA in LBPA was similar to that in other phospholipids. Specific incorporation of DHA into LBPA was also observed in baby hamster kidney fibroblasts, although LBPA in these cells contains very low endogenous levels of DHA in normal growth conditions. Our resuIts, together with published observations, suggest that the specific incorporation of DHA into LBPA is a common phenomenon in mammalian cells. The physiological significance of DHA-enriched LBPA is discussed.

Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses

“…In alveolar macrophages, BMP predominantly contains n-6 fatty acids, such as linoleic acid (18:2) and arachidonic acid (20:4) ( 75,76 ). Interestingly, DHA (C22:6, n-3) comprises a signifi cant portion of BMP fatty acids in many cell types in drug-induced phospholipidosis, and also in many LSDs ( 22,(70)(71)(72)(73)(77)(78)(79)(80)(81)(82). We also found that DHA was a major fatty acid species in BMP from the brains of mice, cats, and bears with gangliosidosis.…”

“…C18:1 is a major BMP fatty acid in many cell types (69)(70)(71)(72)(73)(74). In alveolar macrophages, BMP predominantly contains n-6 fatty acids, such as linoleic acid (18:2) and arachidonic acid (20:4) ( 75,76 ).…”

De novo biosynthesis of the late endosome lipid, bis(monoacylglycero)phosphate

“…In steady-state labeling, lymphoblasts were maintained at a density of ,10 6 cells/ml and labeled in complete medium containing 32 Pi (10 mCi/ml) for 3 days at 37jC. CHO cells were seeded in 100 mm diameter dishes and cultured to confluence in complete medium containing 32 Pi (10 mCi/ml) for 1 or 3 days at 33, 37, or 40jC.…”

“…CHO cells were seeded in 100 mm diameter dishes and cultured to confluence in complete medium containing 32 Pi (10 mCi/ml) for 1 or 3 days at 33, 37, or 40jC. At the end, cells were washed twice with PBS and harvested by centrifugation (lymphoblasts) or scraping (CHO cells).…”

“…In fact, it is considered that in macrophages, BMP is not synthesized de novo but rather derives from exogenous PG (28,29). Whereas the glycerol phosphate backbone of BMP displayed a slow turnover, its esterified fatty acids appeared to turn over rapidly through a mechanism of deacylation-reacylation, which is important for its remodeling (24,30) and could account for the efficient incorporation of exogenous polyunsaturated fatty acids into BMP (29,31,32). To explain the mechanism leading to the specific stereoconversion of the glycerol backbone of PG as well as the fatty acid remodeling, Waite and colleagues (24)(25)(26) proposed a possible pathway for the conversion of PG to BMP in RAW macrophages.…”