Post-translational Transformation of Methionine to Aspartate Is Catalyzed by Heme Iron and Driven by Peroxide

Strader, Michael Brad; Hicks, Wayne; Kassa, Tigist; Singleton, Eileen W.; Soman, Jayashree; Olson, John S.; Weiss, Mitchell J.; Mollan, Todd L.; Wilson, Michael T.; Alayash, Abdu I.

doi:10.1074/jbc.m114.568980

Cited by 27 publications

(38 citation statements)

References 46 publications

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“…The autoxidation rate constants (over 8 h) for the two proteins are reported in Table 1. The k auto (where auto is autoxidation) for HbAO 2 is around 0.065 h Ϫ1 , in agreement with previously reported rates by our group under similar conditions (18), and the rate for HbSO 2 was 0.17 h Ϫ1 , ϳ2-fold faster than that of HbA in agreement with early and more recent reports (3,35). Autoxidation rates for both proteins were reduced by more than 50% with the use of 200 units of catalase in each sample.…”

Section: Autoxidation and Oxidative Reactions Of Hemoglobins-supporting

confidence: 81%

“…For the verification of the ferryl intermediate, 2 mM sodium sulfide (Na 2 S) was added to transform ferryl Hb to sulfhemoglobin (sulfHb). Upon the addition of sulfide, the iron in ferryl Hb is reduced to the ferric state, and at the same time, sulfur is incorporated into the porphyrin ring, which can be monitored by the appearance of an absorbance band at 620 nm (18). A stock solution of 2 mM Na 2 S in a buffer solution was prepared for this purpose by dry weight using a molar mass of 240.18 g/mol for Na 2 S. The concentration of sulfHb was calculated using the extinction coefficient of sulfheme, ⑀620 nm ϭ 24.0 mM Ϫ1 (28).…”

Section: Methodsmentioning

confidence: 99%

“…LC-MS/MS Analysis-All Hb samples were tryptically digested, desalted, and analyzed by mass spectrometry using a previously described method (18). Briefly, tryptic peptides were analyzed by reverse phase-liquid chromatography mass spectrometry (RP LC/MS/MS) using an Easy nLC II Proxeon nanoflow HPLC system coupled on line to a Q-Exactive Orbitrap mass spectrometer (Thermo Scientific).…”

Section: Methodsmentioning

confidence: 99%

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Sickle Cell Hemoglobin in the Ferryl State Promotes βCys-93 Oxidation and Mitochondrial Dysfunction in Epithelial Lung Cells (E10)

Kassa

Jana

Strader

et al. 2015

Journal of Biological Chemistry

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131

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Background: HbS oxidation is recognized as an important element in the pathophysiology of sickle cell disease. Results: The ferric/ferryl redox cycle of HbS is compromised. Conclusion: The inability of ferryl HbS to revert back results in oxidative damage and mitochondrial dysfunction in lung epithelial cells. Significance: These oxidative pathways may contribute to the vasculopathy in sickle cell disease and can be targeted with antioxidants.

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Section: Autoxidation and Oxidative Reactions Of Hemoglobins-supporting

confidence: 81%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Sickle Cell Hemoglobin in the Ferryl State Promotes βCys-93 Oxidation and Mitochondrial Dysfunction in Epithelial Lung Cells (E10)

Kassa

Jana

Strader

et al. 2015

Journal of Biological Chemistry

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131

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“…Stroma-free human adult Hb (HbA) used for in vitro studies was isolated from whole blood as reported earlier [33]. The isolated Hb was further purified on Superdex 200 column to remove catalase.…”

Section: Methodsmentioning

confidence: 99%

Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease

Chintagari

Nguyen

Belcher

et al. 2015

Blood Cells, Molecules, and Diseases

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Sickle cell disease (SCD), a hereditary hemolytic disorder is characterized by chronic hemolysis, oxidative stress, vaso-occlusion and end-organ damage. Hemolysis releases toxic cell-free hemoglobin (Hb) into circulation. Under physiologic conditions, plasma Hb binds to haptoglobin (Hp) and forms Hb-Hp dimers. The dimers bind to CD163 receptors on macrophages for further internalization and degradation. However, in SCD patients plasma Hp is depleted and free Hb is cleared primarily by proximal tubules of kidneys. Excess free Hb in plasma predisposes patients to renal damage. We hypothesized that administration of exogenous Hp reduces Hb-mediated renal damage. To test this hypothesis, human renal proximal tubular cells (HK-2) were exposed to HbA (50 μM heme) for 24 hours. HbA increased the expression of heme oxygenase-1 (HO-1), an enzyme which degrades heme, reduces heme-mediated oxidative toxicity, and confers cytoprotection. Similarly, infusion of HbA (32 μM heme/kg) induced HO-1 expression in kidneys of SCD mice. Immunohistochemistry confirmed the increased HO-1 expression in the proximal tubules of the kidney. Exogenous Hp attenuated the HbA-induced HO-1 expression in vitro and in SCD mice. Our results suggest that Hb-mediated oxidative toxicity may contribute to renal damage in SCD and that Hp treatment reduces heme/iron toxicity in the kidneys following hemolysis.

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“…O 2 to the methionine converts the amino acid into asparagine (106). Irreversible oxidation of β Cys93 occurs, up to two thirds of β Cys93 is oxidized with ~10 fold excess of H 2 O 2 (55).…”

mentioning

confidence: 99%

Redox and Peroxidase Activities of the Hemoglobin Superfamily: Relevance to Health and Disease

Reeder

2017

Antioxidants & Redox Signaling

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Post-translational Transformation of Methionine to Aspartate Is Catalyzed by Heme Iron and Driven by Peroxide

Cited by 27 publications

References 46 publications

Sickle Cell Hemoglobin in the Ferryl State Promotes βCys-93 Oxidation and Mitochondrial Dysfunction in Epithelial Lung Cells (E10)

Sickle Cell Hemoglobin in the Ferryl State Promotes βCys-93 Oxidation and Mitochondrial Dysfunction in Epithelial Lung Cells (E10)

Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease

Redox and Peroxidase Activities of the Hemoglobin Superfamily: Relevance to Health and Disease

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