Selective decrease of bis(monoacylglycero)phosphate content in macrophages by high supplementation with docosahexaenoic acid

Abstract

Bis(monoacylglycero)phosphate (BMP) is a unique phospholipid (PL) preferentially found in late endosomal membranes, where it forms specialized lipid domains. Recently, using cultured macrophages treated with anti-BMP antibody, we showed that BMP-rich domains are involved in cholesterol homeostasis. We had previously stressed the high propensity of BMP to accumulate docosahexaenoic acid (DHA), compared with other PUFAs. Because phosphatidylglycerol (PG) was reported as a precursor for BMP synthesis in RAW macrophages, we examined the effects of PG supplementation on both FA composition and amount of BMP in this cell line. Supplementation with dioleoyl-PG (18:1/18:1-PG) induced BMP accumulation, together with an increase of oleate proportion. Supplementation with high concentrations of didocosahexaenoyl-PG (22:6/22:6-PG) led to a marked enrichment of DHA in BMP, resulting in the formation of diDHA molecular species. However, the amount of BMP was selectively decreased. Similar effects were observed after supplementation with high concentrations of nonesterified DHA. Addition of vitamin E prevented the decrease of BMP and further increased its DHA content. Supplementation with 22:6/22:6-PG promoted BMP accumulation with an enhanced proportion of 22:6/22:6-BMP. DHA-rich BMP was significantly degraded after cell exposure to oxidant conditions, in contrast to oleic acid-rich BMP, which was not affected. Using a cell-free system, we showed that 22:6/22:6-BMP is highly oxidizable and partially protects cholesterol oxidation, compared with 18:1/18:1-BMP. Our data suggest that high DHA content in BMP led to specific degradation of this PL, possibly through the diDHA molecular species, which is very prone to peroxidation and, as such, a potential antioxidant in its immediate

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 ).…”

Exosomes as intercellular signalosomes and pharmacological effectors

“…___________________________________________________________________________ 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 The lysophospholipid named LBPA (lysobis-phosphatidic acid), also called BMP (bis-(monoacylglycero)-phosphate) starts to appear at the stage of MVB along the endocytic track, whereas its precursor, phosphatidylglycerol (PG) is biosynthesized in the mitochondria. Exogenous PG can be converted into LBPA in the MVB [28]. LBPA regulates the ILV turn-over within the MVB [27].…”

“…LBPA is biosynthesized from phosphatidylglycerol (PG) whose biosynthesis occurs in the mitochondria. PG would then be transported to the MVB (Fig 2) which appears to contain the conversion machinery of PG into LBPA since adding PG-containing liposomes in the endocytic track enhances the amount of LBPA recovered in MVB [28].…”

Heat Shock Protein 70.1 (Hsp70.1) Affects Neuronal Cell Fate by Regulating Lysosomal Acid Sphingomyelinase

“…Bouvier et al (38) found that the C 22:6 /C 22:6 species of BMP was highly sensitive to oxidative stress, showing a significant decrease in macrophages after exposure to oxidative stresses, although many studies demonstrated the dramatic increase of BMP levels in the tissue of animals and humans with the lysosomal disorder, such as Niemann-Pick C disease, certain druginduced lipidosis, and anti-phospholipid syndrome (39,40). We carried out LC/MS analysis to measure the BMP levels, as compared with our current quantitative BMP measurement.…”