title: The interaction of actinide and lanthanide ions with hemoglobin and its relevance to human and environmental toxicology.
abstract: Due to increasing use of lanthanides/actinides in nuclear and civil applications, understanding the impact of these metal ions on human health and environment is a growing concern. Hemoglobin (Hb), which occurs in all the kingdom of living organism, is the most abundant protein in human blood. In present study, effect of lanthanides and actinides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] on the structure and function of Hb has been investigated. Results showed that these metal ions, except Ce(IV) interacted with carbonyl and amide groups of Hb, which resulted in the loss of its alpha-helix conformation. However, beyond 75μM, these ions affected heme moiety. Metal-heme interaction was found to affect oxygen-binding of Hb, which seems to be governed by their closeness with the charge-to-ionic-radius ratio of iron(III). Consistently, Ce(IV) being closest to iron(III), exhibited a greater effect on heme. Binding constant and binding stoichiometry of Th(IV) were higher than that of U(VI). Experiments using aquatic midge Chironomus (possessing human homologous Hb) and human blood, further validated metal-Hb interaction and associated toxicity. Thus, present study provides a biochemical basis to understand the actinide/lanthanide-induced interference in heme, which may have significant implications for the medical and environmental management of lanthanides/actinides toxicity.
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India. Electronic address: amitk@barc.gov.in.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: Manjoor
authors.initials: M
authors.lastname: Ali
authors.affiliation: Chemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: Raghumani S
authors.initials: RS
authors.lastname: Ningthoujam
authors.affiliation: Department of Zoology, Savitribai Phule Pune University, Pune 411 007, Mumbai, India.
authors.forename: Pallavi
authors.initials: P
authors.lastname: Gaikwad
authors.affiliation: Solid State, Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: Mukesh
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Department of Zoology, Savitribai Phule Pune University, Pune 411 007, Mumbai, India.
authors.forename: Bimalendu B
authors.initials: BB
authors.lastname: Nath
authors.affiliation: Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.
authors.forename: Badri N
authors.initials: BN
authors.lastname: Pandey
mesh_terms: D000818:Animals; D002563:Cerium / Q000633:toxicity*; D002683:Chironomidae; D054750:Ecotoxicology; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007811:Lanthanum / Q000633:toxicity*; D007814:Larva; D010100:Oxygen / Q000378:metabolism; D013910:Thorium / Q000633:toxicity*; D014501:Uranium / Q000633:toxicity*
chemical_list: D006454:Hemoglobins; D002563:Cerium; D014501:Uranium; D013910:Thorium; D007811:Lanthanum; D010100:Oxygen
keywords: Hemoglobin; Metal-protein binding; Structural and functional alterations