Zinc binding reverses the calcium‐induced arachidonic acid‐binding capacity of the S100A8/A9 protein complex

Kerkhoff, Claus; Vogl, Thomas; Nacken, Wolfgang; Sopalla, Claudia; Sorg, Clemens

doi:10.1016/s0014-5793(99)01322-8

Cited by 61 publications

(62 citation statements)

References 35 publications

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“…However, reversal of growth inhibition by Zn supplements is by itself insufficient to demonstrate mechanisms of CP toxicity. The added Zn might also bind to CP and alter its oligomerization state or structure and affect CP activity independent of metal withholding (33,36,48,49). To definitely test whether Zn supplements work by correcting Zn starvation stress in C. albicans, we examined biomarkers of Zn deprivation.…”

Section: Resultsmentioning

confidence: 99%

“…As mentioned above, Cu is another important micronutrient for microbes, particularly eukaryotic microbes (2). To date, CP binding to Cu has not been reported, although fluorescence studies suggest that Cu can induce conformational changes in CP (36), and other S100 proteins, including S100B, S100A12, and S100A13, have been shown to bind this metal ion (37)(38)(39)(40), raising the possibility of a role for CP in Cu sequestration.…”

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confidence: 99%

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Role of Calprotectin in Withholding Zinc and Copper from Candida albicans

et al. 2018

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The opportunistic fungal pathogen Candida albicans acquires essential metals from the host, yet the host can sequester these micronutrients through a process known as nutritional immunity. How the host withholds metals from C. albicans has been poorly understood; here we examine the role of calprotectin (CP), a transition metal binding protein. When CP depletes bioavailable Zn from the extracellular environment, C. albicans strongly upregulates ZRT1 and PRA1 for Zn import and maintains constant intracellular Zn through numerous cell divisions. We show for the first time that CP can also sequester Cu by binding Cu(II) with subpicomolar affinity. CP blocks fungal acquisition of Cu from serum and induces a Cu starvation stress response involving SOD1 and SOD3 superoxide dismutases. These transcriptional changes are mirrored when C. albicans invades kidneys in a mouse model of disseminated candidiasis, although the responses to Cu and Zn limitations are temporally distinct. The Cu response progresses throughout 72 h, while the Zn response is short-lived. Notably, these stress responses were attenuated in CP null mice, but only at initial stages of infection. Thus, Zn and Cu pools are dynamic at the hostpathogen interface and CP acts early in infection to restrict metal nutrients from C. albicans.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Role of Calprotectin in Withholding Zinc and Copper from Candida albicans

et al. 2018

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“…Studies have shown that the antifungal ability of calprotectin is reversible upon addition of Zn 2ϩ (13,19,20,23). Zn binding to calprotectin leads to conformational changes that alter its ability to bind arachidonic acid (8), but it is unclear how this affects its antimicrobial functions. Multiple studies have shown that the mechanism of the antimicrobial action of calprotectin is sequestration or deprivation of Zn (3,21,22).…”

Section: Discussionmentioning

confidence: 99%

Calprotectin, an Abundant Cytosolic Protein from Human Polymorphonuclear Leukocytes, Inhibits the Growth ofBorrelia burgdorferi

2003

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We previously showed that numerous polymorphonuclear leukocyte (PMN) granule components efficiently kill Borrelia burgdorferi, the agent of Lyme disease. In addition, motile, granule-poor cytoplasts (U-Cyt) from human blood PMN can exert anti-Borrelia activity against opsonized B. burgdorferi independently of oxidative mechanisms. Here we show that lysates of U-Cyt also possess anti-Borrelia activity, a portion of which comes from the abundant cytosolic protein calprotectin. The anti-Borrelia activity of U-Cyt lysates and recombinant calprotectin was partially or completely reversed by specific antibody to calprotectin and by Zn 2؉ , a cation essential for the growth of B. burgdorferi and known to inhibit the antimicrobial activity of calprotectin. Quantitative microscopic and regrowth assays revealed that calprotectin acted in a bacteriostatic fashion against B. burgdorferi. We conclude that calprotectin, a potent bacteriostatic agent from a cell primarily recognized for its oxidative and granular antibacterial mechanisms, may play a modulatory role in infection by the Lyme spirochete, particularly at sites of acute inflammation.

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“…The plasmids pRc-CMV-MRP8, pRc-CMV-MRP14, and pRc-CMV-GFP were kindly provided by H. Perron (BioMerieux, Marcy l'Etoile, France). Human recombinant MRP8 and MRP14 (28,29) were a generous gift from Dr. C. Kerkhoff (Institute of Experimental Dermatology, University of Mü nster, Mü nster, Germany). The cDNA encoding p47 phox cloned into the plasmid pGEX-2T was kindly provided by A.W.…”

Section: Methodsmentioning

confidence: 99%

“…A mixture (1/1) of recombinant MRP8 and MRP14 (rMRP8/rMRP14), prepared in E. coli (28,29) and preloaded with calcium, was used instead of MRP8/MRP14 purified from neutrophil cytosol, in the reconstitution experiment that was performed with an optimal amount of purified cytochrome b 558 and cytosol from EBV-B lymphocytes. Having rMRP8/rMRP14 in the system induced a 50% increase in reconstituted oxidase activity (88 Ϯ 7 versus 60 Ϯ 5 mol of O 2 .…”

Section: Effect Of Recombinant Mrp8 and Mrp14 On Nadph Oxidase Activimentioning

confidence: 99%

Changing the Conformation State of Cytochrome b 558 Initiates NADPH Oxidase Activation

Berthier

Paclet

Lerouge

et al. 2003

Journal of Biological Chemistry

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The phagocyte respiratory burst depends on the NADPH reduction of molecular oxygen and generation of superoxide anion O 2 . upon activation of the cell with soluble (chemotactic factors) or particulate (bacteria or fungi) stimuli (1). The O 2 . -generating NADPH oxidase (EC 1.6.99.6) is a heterogeneous complex compartmentalized in resting cells, between plasma membrane, cytosol, and the cytoskeleton, which assembles at the plasma membrane level once activated. Cytochrome b 558 is the membrane redox core of the oxidase complex, which, after activation, transfers electrons from NADPH to molecular oxygen. It is constituted of gp91 phox (the ␤-catalytic subunit) and p22 phox (␣-subunit), which is necessary in phagocytes to stabilize the 1/1 (␣/␤) heterodimer (2). Three soluble factors, p67 phox , p47 phox , and p40 phox , participate in the activation process, as does the monomeric G protein Rac1/2. Another monomeric G protein, Rap1A, has been identified in the membrane and proposed as a possible regulation factor of the oxidase complex (3, 4). In phagocytes, O 2 . and derivatives are synthesized in large amounts and used as bactericidal tools, but uncontrolled production is also injurious to tissues and triggers inflammatory reactions (5, 6). Phagocyte NADPH oxidase activity is transitory; it is submitted to a strict up-and down-regulation process. Up to now, oxidase activation has been investigated, but the molecular support of down-regulation has not. In fact, the role of a membrane-associated GTPase-activating protein has been described and related to the deactivation of NADPH oxidase (7,8). Recent observations would support an allosteric regulation of NADPH oxidase activity where cytochrome b 558 is the catalytic subunit. In the oxidase assembly, p67 phox is the limiting factor (9 -11). The binding of p67 phox to cytochrome b 558 mediates the transition from an inactive to an active conformation of cytochrome b 558 (11). In the process, p47 phox and Rac1/2 are introduced as positive effectors, whereas the p40 phox function remains undetermined. In chronic granulomatous disease (CGD) 1 , there is no oxidase activity (12).All the components of the phagocyte NADPH oxidase complex are expressed in Epstein-Barr virus-immortalized B lymphocytes. However, in these cells, the activity of stimulated oxidase is 100 times inferior to that of human neutrophils (13). Both neutrophils and EBV-B cells are qualitatively similar in * This work was supported by grants from the Ministère de l'Enseignement supérieur de la Recherche et Technologie, Paris, the Région Rhône Alpes, programme Mobilité Internationale Rhône-Alpes 2001, the Groupement des Entreprises Françaises dans la lutte contre le Cancer, délégation de Grenoble, the Fondation pour la Recherche Médicale, Isère, the Direction Régionale de la Recherche Clinique, and the Association Française, la Ligue Nationale contre le Cancer. We acknowledge the financial support of Mission Physique et Chimie du Vivant (CNRS) and la Fondation pour la Recherche Médicale for atomic force...

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Zinc binding reverses the calcium‐induced arachidonic acid‐binding capacity of the S100A8/A9 protein complex

Cited by 61 publications

References 35 publications

Role of Calprotectin in Withholding Zinc and Copper from Candida albicans

Role of Calprotectin in Withholding Zinc and Copper from Candida albicans

Calprotectin, an Abundant Cytosolic Protein from Human Polymorphonuclear Leukocytes, Inhibits the Growth ofBorrelia burgdorferi

Changing the Conformation State of Cytochrome b 558 Initiates NADPH Oxidase Activation

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