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Oxidation of iron under physiologically relevant conditions in biological fluids from healthy and Alzheimer’s disease subjects Linh Q Lam, Bruce X Wong, Tony Frugier, Qiao-Xin Li, Steven J. Collins, Ashley I Bush, Peter J. Crack, and James A Duce ACS Chem. Neurosci., Just Accepted Manuscript • DOI: 10.1021/acschemneuro.6b00411 • Publication Date (Web): 28 Dec 2016 Downloaded from http://pubs.acs.org on December 29, 2016
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ACS Chemical Neuroscience
Oxidation of iron under physiologically relevant conditions in biological fluids from healthy and Alzheimer’s disease subjects Linh Q. Lam1,2,*, Bruce X. Wong1,3*, Tony Frugier2, Qiao-Xin Li1, Steven J. Collins4, Ashley I. Bush1, Peter J. Crack2,b,# & James A. Duce1,3,a,#.
1
Oxidation Biology Unit, The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia
2
Neuropharmacology Laboratory, Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia
3
School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, West Yorkshire, United Kingdom 4
Department of Medicine, Royal Melbourne Hospital, The University of Melbourne, Parkville, Victoria, Australia *,# These authors contributed equally to the manuscript
Correspondence to: a
Co-corresponding: School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, North Yorkshire, United Kingdom; E-mail:
[email protected] b
Co-corresponding: Neuropharmacology Laboratory, Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, Victoria, Australia. Email:
[email protected] Running title: Physiological ferroxidase in biological fluid Character count for the title: 126 Character count for the running title: 45 Word count for abstract: 104 Word count for text (inc figure legends): 4175 Total number of references: 22 Total number of Tables/Figures: 5
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ACS Chemical Neuroscience
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ABSTRACT Ferroxidase activity has been reported to be altered in various biological fluids in neurodegenerative disease, but the sources contributing to the altered activity are uncertain. Here we assay fractions of serum and cerebrospinal fluid with a newlyvalidated triplex ferroxidase assay. Our data indicate that while ceruloplasmin, a multicopper ferroxidase, is the predominant source of serum activity, activity in CSF predominantly derives from a
