title: Interaction of apoNeuroglobin with heme-Aβ complexes relevant to Alzheimer's disease.
abstract: Heme-Aβ complexes are known to produce toxic partially reduced oxygen species (PROS), catalyze oxidation of neurotransmitters and have been associated with Alzheimer's disease (AD). Neuroglobin (Ngb) play a crucial neuroprotective role against oxidative damage, hypoxic injuries, stroke and apoptosis of neuronal cells. In this study, the interaction of heme-Aβ with apoNeuroglobin (apoNgb) has been investigated using a combination of spectroscopic techniques. Absorption and resonance Raman data confirm that apoNgb can uptake heme from heme-Aβ and constitute a six-coordinate low-spin ferric heme-active site identical to that of Ngb. ApoNgb can also uptake heme from reduced heme-Aβ resulting in the formation of ferrous Ngb. The rate of the heme transfer reaction has been found to be of the order of 10(6) M(-1) s(-1). The reaction is faster for oxidized heme-Aβ than the reduced form. The amount of PROS formation by heme-Aβ complexes has been found to diminish drastically after reaction with apoNgb. ApoNgb can also sequester ligand-bound heme from heme-Aβ, e.g., the CO-bound heme from heme-Aβ-CO complex resulting in the formation of Ngb-CO complex. Additionally, ApoNgb can sequester heme from self-assembled monolayer (SAM) of surface-bound heme-Aβ formed over Au surface. This heme sequestration by apoNgb from heme-Aβ not only diminishes heme-induced toxicity but more significantly it produces Ngb which has well-documented neuroprotective role and can thereby potentially reduce risks associated with AD.
authors: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700032, India.
authors: Manas
authors: M
authors: Seal
authors: Sheetal
authors: S
authors: Uppal
authors: Suman
authors: S
authors: Kundu
authors: Somdatta Ghosh
authors: SG
authors: Dey
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D056831:Coordination Complexes / Q000737:chemistry / Q000378:metabolism*; D005914:Globins / Q000737:chemistry / Q000378:metabolism*; D006418:Heme / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D018625:Microscopy, Atomic Force; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D000078787:Neuroglobin; D010084:Oxidation-Reduction
chemical_list: D016229:Amyloid beta-Peptides; D056831:Coordination Complexes; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D006418:Heme; D005914:Globins; D006861:Hydrogen Peroxide