Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood

Meiling Lu, Hailin Wang, Xing Fang Li, Xiufen Lu, William R. Cullen, Lora L Arnold, Samuel Monroe Cohen, X. Chris Le

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Four trivalent arsenic species, inorganic arsenite (iAsIII), monomethylarsonous acid (MMAIII), dimethylarsinous acid (DMA III), and phenylarsine oxide (PhAsIIIO), have shown increasing binding affinity with the hemoglobin (Hb) of rats and humans. The binding stoichiometry was consistent with the number of reactive cysteine residues in the α and β chains of Hb. Comparing the binding affinity of rat Hb and human Hb for the same trivalent arsenic species, rat Hb was 3-16 times stronger than human Hb as demonstrated by their apparent binding constants. Comparative experiments involving incubation of human and rat red blood cells (RBC) with iAsIII, MMAIII, and DMA III showed that 15-30-fold more arsenic species were bound to the Hb of rat RBC than that of human RBC. In vivo experiments using rats fed with an arsenic-supplemented diet showed that arsenic in RBC of the rats was predominantly found in the protein-bound form. Further characterization by nanoelectrospray mass spectrometry of the arsenic species in the RBC of these rats confirmed that most arsenic was bound to the α chain of Hb. Taken together, these results suggest that the stronger binding affinity of these arsenic species to rat Hb is responsible for the accumulation of arsenic in rat blood. The results provide a chemical basis to explain the previously observed intriguing difference in the retention of arsenic in the human and the rat. The techniques and approaches described can be applied to the studies of arsenic interactions with other functional proteins.

Original languageEnglish (US)
Pages (from-to)1733-1742
Number of pages10
JournalChemical Research in Toxicology
Volume17
Issue number12
DOIs
StatePublished - Dec 1 2004

Fingerprint

Arsenic
Rats
Hemoglobins
Blood
Erythrocytes
Cells
Dynamic mechanical analysis
Nutrition
Stoichiometry
Mass spectrometry
Cysteine
Mass Spectrometry
Proteins
Experiments
Diet

ASJC Scopus subject areas

  • Toxicology

Cite this

Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood. / Lu, Meiling; Wang, Hailin; Li, Xing Fang; Lu, Xiufen; Cullen, William R.; Arnold, Lora L; Cohen, Samuel Monroe; Le, X. Chris.

In: Chemical Research in Toxicology, Vol. 17, No. 12, 01.12.2004, p. 1733-1742.

Research output: Contribution to journalArticle

Lu, Meiling ; Wang, Hailin ; Li, Xing Fang ; Lu, Xiufen ; Cullen, William R. ; Arnold, Lora L ; Cohen, Samuel Monroe ; Le, X. Chris. / Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood. In: Chemical Research in Toxicology. 2004 ; Vol. 17, No. 12. pp. 1733-1742.
@article{e011f8d7b13c4babb24a72270789e788,
title = "Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood",
abstract = "Four trivalent arsenic species, inorganic arsenite (iAsIII), monomethylarsonous acid (MMAIII), dimethylarsinous acid (DMA III), and phenylarsine oxide (PhAsIIIO), have shown increasing binding affinity with the hemoglobin (Hb) of rats and humans. The binding stoichiometry was consistent with the number of reactive cysteine residues in the α and β chains of Hb. Comparing the binding affinity of rat Hb and human Hb for the same trivalent arsenic species, rat Hb was 3-16 times stronger than human Hb as demonstrated by their apparent binding constants. Comparative experiments involving incubation of human and rat red blood cells (RBC) with iAsIII, MMAIII, and DMA III showed that 15-30-fold more arsenic species were bound to the Hb of rat RBC than that of human RBC. In vivo experiments using rats fed with an arsenic-supplemented diet showed that arsenic in RBC of the rats was predominantly found in the protein-bound form. Further characterization by nanoelectrospray mass spectrometry of the arsenic species in the RBC of these rats confirmed that most arsenic was bound to the α chain of Hb. Taken together, these results suggest that the stronger binding affinity of these arsenic species to rat Hb is responsible for the accumulation of arsenic in rat blood. The results provide a chemical basis to explain the previously observed intriguing difference in the retention of arsenic in the human and the rat. The techniques and approaches described can be applied to the studies of arsenic interactions with other functional proteins.",
author = "Meiling Lu and Hailin Wang and Li, {Xing Fang} and Xiufen Lu and Cullen, {William R.} and Arnold, {Lora L} and Cohen, {Samuel Monroe} and Le, {X. Chris}",
year = "2004",
month = "12",
day = "1",
doi = "10.1021/tx049756s",
language = "English (US)",
volume = "17",
pages = "1733--1742",
journal = "Chemical Research in Toxicology",
issn = "0893-228X",
publisher = "American Chemical Society",
number = "12",

}

TY - JOUR

T1 - Evidence of hemoglobin binding to arsenic as a basis for the accumulation of arsenic in rat blood

AU - Lu, Meiling

AU - Wang, Hailin

AU - Li, Xing Fang

AU - Lu, Xiufen

AU - Cullen, William R.

AU - Arnold, Lora L

AU - Cohen, Samuel Monroe

AU - Le, X. Chris

PY - 2004/12/1

Y1 - 2004/12/1

N2 - Four trivalent arsenic species, inorganic arsenite (iAsIII), monomethylarsonous acid (MMAIII), dimethylarsinous acid (DMA III), and phenylarsine oxide (PhAsIIIO), have shown increasing binding affinity with the hemoglobin (Hb) of rats and humans. The binding stoichiometry was consistent with the number of reactive cysteine residues in the α and β chains of Hb. Comparing the binding affinity of rat Hb and human Hb for the same trivalent arsenic species, rat Hb was 3-16 times stronger than human Hb as demonstrated by their apparent binding constants. Comparative experiments involving incubation of human and rat red blood cells (RBC) with iAsIII, MMAIII, and DMA III showed that 15-30-fold more arsenic species were bound to the Hb of rat RBC than that of human RBC. In vivo experiments using rats fed with an arsenic-supplemented diet showed that arsenic in RBC of the rats was predominantly found in the protein-bound form. Further characterization by nanoelectrospray mass spectrometry of the arsenic species in the RBC of these rats confirmed that most arsenic was bound to the α chain of Hb. Taken together, these results suggest that the stronger binding affinity of these arsenic species to rat Hb is responsible for the accumulation of arsenic in rat blood. The results provide a chemical basis to explain the previously observed intriguing difference in the retention of arsenic in the human and the rat. The techniques and approaches described can be applied to the studies of arsenic interactions with other functional proteins.

AB - Four trivalent arsenic species, inorganic arsenite (iAsIII), monomethylarsonous acid (MMAIII), dimethylarsinous acid (DMA III), and phenylarsine oxide (PhAsIIIO), have shown increasing binding affinity with the hemoglobin (Hb) of rats and humans. The binding stoichiometry was consistent with the number of reactive cysteine residues in the α and β chains of Hb. Comparing the binding affinity of rat Hb and human Hb for the same trivalent arsenic species, rat Hb was 3-16 times stronger than human Hb as demonstrated by their apparent binding constants. Comparative experiments involving incubation of human and rat red blood cells (RBC) with iAsIII, MMAIII, and DMA III showed that 15-30-fold more arsenic species were bound to the Hb of rat RBC than that of human RBC. In vivo experiments using rats fed with an arsenic-supplemented diet showed that arsenic in RBC of the rats was predominantly found in the protein-bound form. Further characterization by nanoelectrospray mass spectrometry of the arsenic species in the RBC of these rats confirmed that most arsenic was bound to the α chain of Hb. Taken together, these results suggest that the stronger binding affinity of these arsenic species to rat Hb is responsible for the accumulation of arsenic in rat blood. The results provide a chemical basis to explain the previously observed intriguing difference in the retention of arsenic in the human and the rat. The techniques and approaches described can be applied to the studies of arsenic interactions with other functional proteins.

UR - http://www.scopus.com/inward/record.url?scp=10844245622&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10844245622&partnerID=8YFLogxK

U2 - 10.1021/tx049756s

DO - 10.1021/tx049756s

M3 - Article

C2 - 15606151

AN - SCOPUS:10844245622

VL - 17

SP - 1733

EP - 1742

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

SN - 0893-228X

IS - 12

ER -