Acute catabolism of leukocyte lipid bodies: Characterization of a nordihydroguaiaretic acid (NDGA)-induced proteasomal-dependent model

• Published in: Prostaglandins, leukotrienes and essential fatty acids Vol. 171; p. 102320
• Main Authors: de Lira, Maria N., Bolini, Lukas, Amorim, Natália R.T., Silva-Souza, Hercules A., Diaz, Bruno L., Canetti, Claudio, Persechini, Pedro M., Bandeira-Melo, Christianne
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.08.2021
• Subjects: Animals; Eosinophils; Eosinophils - drug effects; Eosinophils - metabolism; Leukocytes - drug effects; Leukocytes - metabolism; Lipid droplets; Lipid Droplets - drug effects; Lipid Droplets - metabolism; Lipoxygenase Inhibitors - pharmacology; Macrophages; Macrophages - drug effects; Macrophages - metabolism; Masoprocol - pharmacology; Mice; NDGA; Neutrophils; Neutrophils - drug effects; Neutrophils - metabolism; Proteasome; Proteasome Endopeptidase Complex - drug effects; Proteasome Endopeptidase Complex - metabolism; NDGA; Macrophages; Lipid droplets; Neutrophils; Eosinophils; Proteasome
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2021.102320

•NDGA induces rapid reduction of cytoplasmic lipid body content within macrophages by a mechanism dependent on proteasomal-driven catabolic activity.•Proteasomal-driven lipid body catabolism mediates lipid body number reduction associated with LPS-induced temporal kinetics of lipid body alterations within macrophages.•NDGA-induced lipid body catabolism within macrophages is not related to ATP secretion, calcium influx or 5-LO inhibition.•NDGA also evokes proteasomal-driven lipid body catabolism in neutrophils and eosinophils. Cytoplasmic availability of leukocyte lipid bodies is controlled by a highly regulated cycle of opposing biogenesis- and catabolism-related events. While leukocyte biogenic machinery is well-characterized, lipid body catabolic mechanisms are yet mostly unknown. Here, we demonstrated that nordihydroguaiaretic acid (NDGA) very rapidly decreases the numbers of pre-formed lipid bodies within lipid body-enriched cytoplasm of mouse leukocytes – macrophages, neutrophils and eosinophils. NDGA mechanisms driving leukocyte lipid body disappearance were not related to loss of cell viability, 5-lipoxygenase inhibition, ATP autocrine/paracrine activity, or biogenesis inhibition. Proteasomal-dependent breakdown of lipid bodies appears to control NDGA-driven leukocyte lipid body reduction, since it was Bortezomib-sensitive in macrophages, neutrophils and eosinophils. Our findings unveil an acute NDGA-triggered lipid body catabolic event – a novel experimental model for the still neglected research area on leukocyte lipid body catabolism, additionally favoring further insights on proteasomal contribution to lipid body breakdown.