One ring to rule them all: Trafficking of heme and heme synthesis intermediates in the metazoans

Hamza, Iqbal; Dailey, Harry A.

doi:10.1016/j.bbamcr.2012.04.009

Cited by 210 publications

(232 citation statements)

References 239 publications

(313 reference statements)

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“…In the terminal step in heme biosynthesis in the erythroblast, the enzyme ferrochelatase (EC 4.99.1.1) inserts ferrous iron into PPIX to produce heme [1]. Divalent iron is the preferred substrate for erythroid ferrochelatase, but divalent zinc can serve as an alternative, and small amounts of ZnPP are formed under physiological conditions [2].…”

Section: Introductionmentioning

confidence: 99%

Dual‐wavelength excitation for fluorescence‐based quantification of zinc protoporphyrin IX and protoporphyrin IX in whole blood

Hennig

Gruber

Vogeser

et al. 2013

Journal of Biophotonics

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Journal of BIOPHOTONICSQuantification of erythrocyte zinc protoporphyrin IX (ZnPP) and protoporphyrin IX (PPIX), individually or jointly, is useful for the diagnostic evaluation of iron deficiency, iron-restricted erythropoiesis, lead exposure, and porphyrias. A method for simultaneous quantification of ZnPP and PPIX in unwashed blood samples is described, using dual-wavelength excitation to effectively eliminate background fluorescence from other blood constituents. In blood samples from 35 subjects, the results of the dualwavelength excitation method and a reference high performance liquid chromatography (HPLC) assay were closely correlated both for ZnPP (r s ¼ 0.943, p < 0.0001; range 37-689 mmol ZnPP/mol heme, 84-1238 nmol/L) and for PPIX (r s ¼ 0.959, p < 0.0001; range 42-4212 mmol PPIX/mol heme, 93-5394 nmol/L). In addition, for ZnPP, the proposed method is compared with conventional single-wavelength excitation and with commercial front-face fluorimetry of washed erythrocytes and whole blood. We hypothesize that dual-wavelength excitation fluorimetry will provide a new approach to the suppression of background fluorescence in blood and tissue measurements of ZnPP and PPIX.

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Section: Introductionmentioning

confidence: 99%

Dual‐wavelength excitation for fluorescence‐based quantification of zinc protoporphyrin IX and protoporphyrin IX in whole blood

Hennig

Gruber

Vogeser

et al. 2013

Journal of Biophotonics

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“…Hemoglobin molecules released into the blood due to hemolysis are bound to haptoglobin and taken up by macrophages. Free heme released from hemoproteins, including hemoglobin, is bound to hemopexin and taken up by macrophages via receptor-mediated endocytosis (Hamza and Dailey 2012;Sheftel et al 2012). At the end of the day, heme-protein complexes are degraded in the endosome-lysosome system, and heme is transferred to the cytoplasm where it is degraded by HO-1 and HO-2, which are bound to the cytoplasmic surface of the endoplasmic reticulum (Fig.…”

Section: Bach1 In the Regulation Of Iron Homeostasis And Oxidative Stmentioning

confidence: 99%

Wearing Red for Signaling: The Heme-Bach Axis in Heme Metabolism, Oxidative Stress Response and Iron Immunology

Igarashi

Watanabe-Matsui

2014

Tohoku J. Exp. Med.

104

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The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of "iron immunology" as the synthesis of the iron metabolism and the immune response.

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“…One member of these multidrug transporters, ABCG2, has been shown to play a major role in the protection of stem cells against toxic compounds. In addition, the ABCB6 protein has been indicated to play a major role in the defense against toxic heme derivatives, while the ABCA1 protein has a key role in the extrusion of excess cellular lipid derivatives, especially cholesterol (see refs (4)(5)(6)(7)(8)(9) ).…”

Section: Supplementary Tablementioning

confidence: 99%

Expression pattern of the human ABC transporters in pluripotent embryonic stem cells and in their derivatives

et al. 2014

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Background: ATP-binding Cassette (ABC) transporters have key roles in various physiological functions as well as providing chemical defense and stress tolerance in human tissues. In this study we have examined the expression pattern of all ABC proteins in pluripotent human embryonic stem cells (hESCs) and in their differentiated progenies. We paid special attention to the cellular expression and localization of multidrug transporter ABC proteins.Methods: Stem cell differentiation was carried out without chemical induction or cell sorting, and specialized cell types were separated mechanically. Cellular features regarding pluripotency and tissue identity, as well as ABC transporter expression were studied by flow cytomtery, immuno-microscopy and qPCR-based low-density arrays.Results: Pluripotent hESCs and differentiated cell types (cardiomyocytes, neuronal cells and mesenchymal stem cells) were distinguished by morphology, immunostaining markers and selected mRNA expression patterns. We found that the mRNA expression levels of the 48 human ABC proteins also clearly distinguished the pluripotent and the respective differentiated cell types. When multidrug and lipid transporter ABC protein expression was examined by using well characterized specific antibodies by flow cytometry and confocal microscopy, the protein expression data corresponded well to the mRNA expression results.Moreover, the cellular localization of these important human ABC transporter proteins could be established in the pluripotent and differentiated hESC derived samples. Conclusions:These studies provide valuable information regarding ABC protein expression in human stem cells and their differentiated offspring. The results may also help to obtain further information concerning the specialized cellular functions of selected ABC transporters.

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One ring to rule them all: Trafficking of heme and heme synthesis intermediates in the metazoans

Cited by 210 publications

References 239 publications

Dual‐wavelength excitation for fluorescence‐based quantification of zinc protoporphyrin IX and protoporphyrin IX in whole blood

Dual‐wavelength excitation for fluorescence‐based quantification of zinc protoporphyrin IX and protoporphyrin IX in whole blood

Wearing Red for Signaling: The Heme-Bach Axis in Heme Metabolism, Oxidative Stress Response and Iron Immunology

Expression pattern of the human ABC transporters in pluripotent embryonic stem cells and in their derivatives

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