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

FEBS Letters

Siems, Werner G.⁴  Arese, Paolo¹  Schwarzer, Evelin²  Müller, Oliver³  Grune, Tilman³ 

[1] Department of Genetics, Biology and Medical Chemistry, University of Torino Medical School, Via Santena 5 bis, 10126 Torino, Italy;Institute of Biochemistry, Humboldt University Medical School (Charité), Berlin, Germany;Clinics of Physical Medicine, Humboldt University Medical School (Charité), Berlin, Germany;Herzog-Julius-Hospital for Rheumatology and Orthopedics, Bad Harzburg, Germany

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;   

DOI  :  10.1016/0014-5793(96)00523-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown