TY - JOUR
T1 - Fe-oxy adducts of heme-Aβ and heme-hIAPP complexes
T2 - Intermediates in ROS generation
AU - Seal, Manas
AU - Mukherjee, Soumya
AU - Dey, Somdatta Ghosh
N1 - Funding Information:
We thank CSIR, India (Grant 01(2764)/13/EMR-II), DST, India (Grant EMR/2015/000392), Government of India and IACS for funding this research. M. S. is thankful to the IACS-integrated PhD program for a Senior Research Fellowship. S. M. acknowledges a research fellowship from CSIR. We thank Dr A. Dey and DST SR/IC-35/2009 (A. D.) for the rR.
Publisher Copyright:
© The Royal Society of Chemistry 2016.
PY - 2016/12
Y1 - 2016/12
N2 - 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-1 and 577 cm-1 for 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.
AB - 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-1 and 577 cm-1 for 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.
UR - http://www.scopus.com/inward/record.url?scp=85003008511&partnerID=8YFLogxK
U2 - 10.1039/c6mt00214e
DO - 10.1039/c6mt00214e
M3 - Article
C2 - 27844077
AN - SCOPUS:85003008511
SN - 1756-5901
VL - 8
SP - 1266
EP - 1272
JO - Metallomics
JF - Metallomics
IS - 12
ER -