β-Hematin (Hemozoin) Mediated Decompostion of Polyunsaturated Fatty Acids to 4-Hydroxy-2-nonenal

Miller, Crystal; Carney, Clare K.; Schrimpe, and Alexandra C.; Wright, David W.

doi:10.1021/ic048821i

Cited by 11 publications

(11 citation statements)

References 26 publications

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“…Importantly, Hz phagocytosis enhances MMP‐9 secretion and pro‐enzyme activity . Because Hz mediates LPO in vitro and LPO species are increased in Hz‐fed monocytes, biologically active LPO products may play a role in Hz‐mediated MMP‐9 dysregulation.…”

Section: Resultsmentioning

confidence: 99%

“…Investigations of the complex composition of native Hz revealed an array of host‐derived and parasite‐derived lipid peroxidation (LPO) species including hydroxyeicosatetraenoic acids (HETEs) and 4‐hydroxynonenal (HNE) . These products are expected to be a consequence of the biomineral's reactivity; purified Hz and its synthetic analogue beta ‐hematin (BH) mediate the non‐enzymatic oxidation of arachidonic acid to HETEs and HNE . Importantly, many LPO species are themselves also biologically active.…”

Section: Introductionmentioning

confidence: 99%

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Impact of 4‐hydroxynonenal on matrix metalloproteinase‐9 regulation in lipopolysaccharide‐stimulated RAW 264.7 cells

Schrimpe‐Rutledge

Fong

Wright

2015

Cell Biochemistry & Function

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Tissue degradation and leukocyte extravasation suggest proteolytic destruction of the extracellular matrix (ECM) during severe malaria. Matrix metalloproteinases (MMPs) play an established role in ECM turnover, and increased MMP-9 protein abundance is correlated with malarial infection. The malaria pigment hemozoin (Hz) is a heme detoxification biomineral that is produced during infection and associated with biologically active lipid peroxidation products such as 4-hydroxynonenal (HNE) adsorbed to its surface. Hz has innate immunomodulatory activity, and many of its effects can be reproduced by exogenously added HNE. Hz phagocytosis enhances MMP-9 expression in monocytes; thus, this study was designed to examine the ability of HNE to alter MMP-9 regulation in activated cells of macrophage lineage. Data show that treatment of lipopolysaccharide-stimulated RAW 264.7 cells with HNE increased MMP-9 secretion and activity. HNE treatment abolished the cognate tissue inhibitor of metalloproteinase-1 protein levels, further decreasing MMP-9 regulation. Phosphorylation of both p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase was induced by HNE, but only p38 MAPK inhibition lessened MMP-9 secretion. These results demonstrate the in vitro ability of HNE to cause MMP-9 dysregulation in an activated cell model. The findings may extend to myriad pathologies associated with lipid peroxidation and elevated MMP-9 levels leading to tissue damage.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Impact of 4‐hydroxynonenal on matrix metalloproteinase‐9 regulation in lipopolysaccharide‐stimulated RAW 264.7 cells

Schrimpe‐Rutledge

Fong

Wright

2015

Cell Biochemistry & Function

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“…The 4-HNE molecule is a highly reactive lipo-peroxidation end-product (Poli et al, 2008) generated by haemozoin-containing parasitized RBCs and residual bodies (Miller et al, 2005;Skorokhod et al, 2007Skorokhod et al, , 2010Schwarzer et al, 2008) and by haemozoin-fed phagocytes (Schwarzer et al, 1996(Schwarzer et al, , 2008Skorokhod et al, 2005Skorokhod et al, , 2010. The 4-HNE binds to extracellular protein domains of the RBC membrane (Skorokhod et al, 2007;Uyoga et al, 2012) and may diffuse to neighbour cells, forming stable 4-HNE-protein conjugates (Uyoga et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Blood oxidative stress markers and Plasmodium falciparum malaria in non‐immune African children

et al. 2014

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SummaryConverging in vitro evidence and clinical data indicate that oxidative stress may play important roles in Plasmodium falciparum malaria, notably in the pathogenesis of severe anaemia. However, oxidative modifications of the red blood cell (RBC)-membrane by 4-hydroxynonenal (4-HNE) and haemoglobin-binding, previously hypothesized to contribute mechanistically to the pathogenesis of clinical malaria, have not yet been tested for clinical significance. In 349 non-immune Mozambican newborns recruited in a double-blind placebo-controlled chemoprophylaxis trial, oxidative markers including 4-HNE-conjugates and membrane-bound haemoglobin were longitudinally assessed from 2Á5 to 24 months of age, at first acute malaria episode and in convalescence. During acute malaria, 4-HNE-conjugates were shown to increase significantly in parasitized and non-parasitized RBCs. In parallel, advanced oxidation protein products (AOPP) rose in plasma. 4-HNE-conjugates correlated with AOPP and established plasma but not with RBC oxidative markers. High individual levels of 4-HNEconjugates were predictive for increased malaria incidence rates in children until 2 years of life and elevated 4-HNE-conjugates in convalescence accompanied sustained anaemia after a malaria episode, indicating 4-HNEconjugates as a novel patho-mechanistic factor in malaria. A second oxidative marker, haemoglobin binding to RBC-membranes, hypothesized to induce clearing of RBCs from circulation, was predictive for lower malaria incidence rates. Further studies will show whether or not higher membrane-haemoglobin values at the first malaria episode may provide protection against malaria.

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“…Hemin aggregates have been shown to produce lipid oxidation products such as 4-hydroxy-2-nonenal in the presence of polyunsaturated fatty acids (Miller, Carney, Schrimpe, & Wright, 2005), TBARS in the presence of arachidonic acid micelles and phospholipid vesicles (Littell et al, 1998), and monohydroxy derivatives of arachidonic and linoleic acids (Schwarzer et al, 2003). Hx inhibited hemin-mediated lipid oxidation in rat microsomes (pH 7.4 and 0.050 mol/L NaCl) (Vincent et al, 1988), and in linoleic acid micelles at pH 6.4 (Gutteridge & Smith, 1988).…”

Section: Discussionmentioning

confidence: 99%

Effects of hemopexin on hemin and hemoglobin-mediated lipid oxidation in washed fish muscle

Grunwald

Richards

2012

LWT - Food Science and Technology

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β-Hematin (Hemozoin) Mediated Decompostion of Polyunsaturated Fatty Acids to 4-Hydroxy-2-nonenal

Cited by 11 publications

References 26 publications

Impact of 4‐hydroxynonenal on matrix metalloproteinase‐9 regulation in lipopolysaccharide‐stimulated RAW 264.7 cells

Impact of 4‐hydroxynonenal on matrix metalloproteinase‐9 regulation in lipopolysaccharide‐stimulated RAW 264.7 cells

Blood oxidative stress markers and Plasmodium falciparum malaria in non‐immune African children

Effects of hemopexin on hemin and hemoglobin-mediated lipid oxidation in washed fish muscle

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