The Toxicities of Native and Modified Hemoglobins

Everse, Johannes; Hsia, Nelson

doi:10.1016/s0891-5849(96)00499-6

Cited by 326 publications

(233 citation statements)

References 165 publications

Supporting

Mentioning

228

Contrasting

Order By: Relevance

“…Pronounced methemoglobinemia causes hemolysis, hypoxia, and cyanosis, and will eventually be fatal. HbFe IV AO is also considered a starting point for detrimental radical chain reactions (leading, e.g., to lipid peroxidation) via superoxide radical anion, NO, and peroxynitrite (22,23). Thus, we strongly endorse the view (24) that ET serves as a safety catch in the autocatalytic oxidation of hemoglobin, or more generally, that ET protects Fig.…”

Section: Discussionmentioning

confidence: 62%

See 1 more Smart Citation

Discovery of the ergothioneine transporter

Gründemann

Harlfinger

Gölz

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

468

482

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 62%

“…Saturation analysis (Fig. 4) of initial rates of OCTN1h-catalyzed uptake revealed a K m of 21 mol͞liter (95% confidence interval, [16][17][18][19][20][21][22][23][24][25][26][27][28], which for a transport protein indicates high affinity. The affinity of OCTN1h for stachydrine was much lower [K i ϭ 270 (210-350) mol͞liter; not shown].…”

Section: Resultsmentioning

confidence: 99%

Discovery of the ergothioneine transporter

Gründemann

Harlfinger

Gölz

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

468

482

View full text Add to dashboard Cite

show abstract

“…As mentioned above, free Hb or oxyHb spontaneously oxidizes to form metHb outside of the RBC and, in general, metHb is more toxic than oxyHb because it loses its heme group more readily [24]. [13,16].…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular or free Hb released from lysed erythrocytes (oxyHb; Fe +2 ) causes injury to endothelial cells [5,59,81] and death of cultured neurons [24,77,83]. It also undergoes spontaneous oxidation to methemoglobin (metHb, Fe +3 ) which loses its heme group more readily than oxyHb [24,69].…”

Section: Oxidized Heme and Damage To Vascular Cellsmentioning

confidence: 99%

“…It also undergoes spontaneous oxidation to methemoglobin (metHb, Fe +3 ) which loses its heme group more readily than oxyHb [24,69]. Oxidized heme is a pro-oxidant that damages vascular cells, where the iron derived from heme becomes available to produce a variety of reactive oxygen species via the Fenton reaction, [46,101] resulting in membrane lipid peroxidation and damage to DNA and proteins [40,47,61].…”

Section: Oxidized Heme and Damage To Vascular Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

Perry

Gearhart

Wiener

et al. 2008

Neurobiology of Aging

View full text Add to dashboard Cite

From a normal human brain phage display library screen we identified the gamma (A)-globin chain of fetal hemoglobin (Hb F) as a protein that bound strongly to Aβ1-42. We showed the oxidized form 1 These authors are co-corresponding authors for all stages of refereeing and publication and contributed equally to this work. Rodney T. Perry; Rm. 210H, 1665 University Blvd.; University of Alabama at Birmingham, Birmingham, USA; Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Disclosure Statement:I so state for myself and on behalf of the other authors on the manuscript, Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease, that we have no conflicts and sources of funding that influence the results of this paper, the data is not published or submitted elsewhere, and that appropriate approval and procedures were used concerning human subjects. I also verify that all authors on this manuscript have reviewed the contents of the manuscript, approve of its contents, and validate the accuracy of the data. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript of adult Hb (metHb A) binds with greater affinity to Aβ1-42 than metHb F. MetHb is more toxic than oxyhemoglobin because it loses its heme group more readily. Free Hb and heme readily damage vascular endothelial cells similar to Alzheimer's disease (AD) vascular pathology. The XmnI polymorphism (C→T) at −158 of the gamma (G)-globin promoter region can contribute to increased Hb F expression. Using family-based association testing, we found a significant protective association of this polymorphism in the NIMH sibling dataset (n=489) in families, with at least two affected and one unaffected sibling (p=0.006), with an age of onset >50 years (p=0.010) and >65 years (p=0.013), and families not homozygous for the APOE4 allele (p=0.041). We hypothesize that Hb F may be less toxic than adult Hb in its interaction with Aβ and may protect against the development of AD.

show abstract

Haematoporphyrin enhances the peroxidase activity of haemoglobin

Sil

Kar

Chakraborti

2000

J. Porphyrins Phthalocyanines

View full text Add to dashboard Cite

The effect of haematoporphyrin, a component of some of the widely used anticancer drugs, on the peroxidase activity of haemoglobin has been studied. Haematoporphyrin increases the haemoglobin-catalysed hydrogen peroxide-mediated oxidation of o-dianisidine or NADH. Spectrophotometric study reveals that an interaction occurs between haemoglobin and haematoporphyrin which leads to a conformational change of the protein. The extent of enhanced peroxidase activity as well as conformational change of the protein vary in a positive manner with the stoichiometric ratio of haematoporphyrin/haemoglobin. An increase in the peroxidase activity of haemoglobin was also observed in the presence of superoxide dismutase, which catalysed the removal of superoxide anion generated during autoxidation of haemoglobin. Possible mechanisms underlying the relation between the conformational change of haemoglobin due to its interaction with haematoporphyrin and the enhanced peroxidase activity are discussed.

show abstract

The Toxicities of Native and Modified Hemoglobins

Cited by 326 publications

References 165 publications

Discovery of the ergothioneine transporter

Discovery of the ergothioneine transporter

Hemoglobin binding to Aβ and HBG2 SNP association suggest a role in Alzheimer's disease

Haematoporphyrin enhances the peroxidase activity of haemoglobin

Contact Info

Product

Resources

About