Increased levels of 4‐hydroxynonenal in human monocytes fed with malarial pigment hemozoin A possible clue for hemozoin toxicity

[摘要]

In human monocytes, lipoperoxides were increased 3-fold at 2 h, 6-fold at 5 h and 7.5-fold at 12 h after hemozoin phagocytosis. 4-Hydroxynonenal (HNE) was also increased, reaching 40 nmol/10¹⁰ cells at 2 h (approximate intracellular concentration [AIE] 8 μM), 230 nmol/10¹⁰ cells at 5 h (AIE 46 μM) and 79 nmol/10¹⁰ cells (AIE 16 μM) at 12 h. A moderate increase in HNE, approx. 20 nmol/10¹⁰ cells (AIE 4 μM) was also observed after phagocytosis of anti-D IgG-opsonized erythrocytes. HNE in unfed controls was approx. 5 nmol/10¹⁰ cells (AIE 1 μM) during the whole incubation period. An increased amount of protein kinase C (PKC)/HNE adduct was demonstrated in hemozoin-fed monocytes. Purified PKC was profoundly inhibited at HNE > 10 μM. The impairment of PKC previously observed in hemozoin-fed monocytes can thus be explained by direct interaction with increased HNE levels.

[学科分类] 生物化学/生物物理

[关键词] 4-Hydroxynonenal;Malaria (Plasmodium falciparum);Hemozoin;Monocyte (human);Phagocytosis;Protein kinase C inhibition;BSA;bovine serum albumin;ECL;enhanced chemiluminescence;HNE;4-hydroxy-2;3-trans-nonenal (4-hydroxynonenal);HPLC;high-performance liquid chromatography;IgG;immunoglobulin G;luminol;5-amino-2;3-dihydro-1;4-phthalazinedione;MIP-1α/-1β;macrophage inflammatory protein-1α/-1β;PKC;protein kinase C;RBC;erythrocytes;SDS-PAGE;sodium dodecyl sulfatepolyacrylamide gel electrophoresis