title: Increased levels of 4-hydroxynonenal in human monocytes fed with malarial pigment hemozoin. A possible clue for hemozoin toxicity.
abstract: 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/10(10) cells at 2 h (approximate intracellular concentration [AIE] 8 microM) 230 nmol/10(10) cells at 5 h (AIE 46 microM) and 79 nmol/10(10) cells (AIE 16 microM) at 12 h. A moderate increase in HNE, approx. 20 nmol/10(10) cells (AIE 4 microM) was also observed after phagocytosis of anti-D IgG-opsonized erythrocytes. HNE in unfed controls was approx. 5 nmol/10(10) cells (AIE 1 microM) 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 microM. The impairment of PKC previously observed in hemozoin-fed monocytes can thus be explained by direct interaction with increased HNE levels.
authors.affiliation: Institute of Biochemistry, Humboldt University Medical School (Charité) Berlin, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schwarzer
authors.forename: O
authors.initials: O
authors.lastname: Müller
authors.forename: P
authors.initials: P
authors.lastname: Arese
authors.forename: W G
authors.initials: WG
authors.lastname: Siems
authors.forename: T
authors.initials: T
authors.lastname: Grune
mesh_terms: D000328:Adult; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D005260:Female; D006420:Hemeproteins / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D010587:Phagocytosis; D010860:Pigments, Biological / Q000378:metabolism* / Q000633:toxicity; D010963:Plasmodium falciparum / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D013997:Time Factors
chemical_list: D000447:Aldehydes; D006420:Hemeproteins; D008054:Lipid Peroxides; D010860:Pigments, Biological; C020753:hemozoin; D011493:Protein Kinase C; C027576:4-hydroxy-2-nonenal