title: Fe-oxy adducts of heme-Aβ and heme-hIAPP complexes: intermediates in ROS generation.
abstract: Iron (Fe) is the most abundant transition metal ion in the human body and its role, in the form of heme, has been implicated in Alzheimer's disease (AD) and type 2 diabetes mellitus (T2Dm). Heme binds both amyloid beta (Aβ) and human islet amyloid polypeptide (hIAPP) to form heme-Aβ and heme-hIAPP complexes, respectively, and form reactive oxygen species (ROS) like H2O2, O2˙-etc., which are known to cause oxidative damage. However the intermediates involved during ROS formation have not yet been isolated. In this study the oxygen bound intermediates of both heme-Aβ(1-16) and heme-hIAPP(1-19) have been isolated and characterized using absorption, EPR and resonance Raman (rR) spectroscopy. Fe-O stretches have been found at 575 cm-1and 577 cm-1for heme-Aβ(1-16) and heme-hIAPP(1-19) respectively. The oxy intermediates are stable at low temperatures. The isolation of the intermediates reveals a mechanistic pathway of ROS generation through the two heme complexes.
authors.affiliation: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India. icsgd@iacs.res.in.
authors.forename: Manas
authors.initials: M
authors.lastname: Seal
authors.affiliation: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India. icsgd@iacs.res.in.
authors.forename: Soumya
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Department of Inorganic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India. icsgd@iacs.res.in.
authors.forename: Somdatta Ghosh
authors.initials: SG
authors.lastname: Dey
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006801:Humans; D058085:Iron Compounds / Q000378:metabolism*; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D058085:Iron Compounds; D058228:Islet Amyloid Polypeptide; D017382:Reactive Oxygen Species; D006418:Heme