This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Changes in the heme environment when the a-hemoglobin stabilizing protein (AHSP) binds to a-hemoglobin (a-Hb), which we have studied by Raman spectroscopy, will be monitored by Fe K-edge XAFS. Such binding is important in prevention of toxic heme precipitation from unstable oxy-a-Hb, but all crystal structures of AHSP:oxy-a-Hb complexes contain mutant Hb and it is not clear whether the structures are the same as with the wild type because they have different reactivities. Fe K-edge XAFS will also be used to study the reactions of myoglobin with H2O2 in cardiac myocytes. Such processes are thought to lead ultimately to cardiovascular disease and XAS will be recorded on snap frozen cell pellets of the myocytes (using previously developed techniques) that are untreated or H2O2-treated and changes in the Mb XAS will be monitored. Cr K-edge XAFS will be recorded on Cr(VI) adducts of phosphatase enzymes (for which there are no structural data), since we have recently shown that anti-diabetic effects of commonly used Cr(III) dietary supplements are likely to be exerted by in-vivo enzymatic oxidation of the Cr(III) dietary supplements to carcinogenic Cr(VI), followed increased insulin activity due to potent Cr(VI) inhibition of phosphatase enzymes We also intend to study the very early stages of the biotransformations of Cr(VI) in human lung cells to complement our recent work in the area.
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