%0 Journal Article
%~ PubMed
%A Whitnall, Megan
%A Rahmanto, Yohan Suryo
%A Huang, Michael L-H
%A Saletta, Federica
%A Lok, Hiu Chuen
%A Gutiérrez, Lucía
%A Lázaro, Francisco J
%A Fleming, Adam J
%A St Pierre, Tim G
%A Mikhael, Marc R
%A Ponka, Prem
%A Richardson, Des R
%T Identification of nonferritin mitochondrial iron deposits in a mouse model of Friedreich ataxia.
%B Proceedings of the National Academy of Sciences
%D 2012
%C United States
%I National Academy of Sciences
%V 109
%N 50
%P 20590-20595
%@ 0027-8424
%X 
%Z FOR Codes: 601


%0 Journal Article
%~ PubMed
%A Lok, Hiu Chuen
%A Suryo Rahmanto, Yohan
%A Hawkins, Clare L
%A Kalinowski, Danuta S
%A Morrow, Charles S
%A Townsend, Alan J
%A Ponka, Prem
%A Richardson, Des R
%T Nitric oxide storage and transport in cells is mediated by glutathione-S-transferase P1-1 and Multidrug Resistant Protein 1 via Dinitrosyl iron complexes.
%B Journal of Biological Chemistry
%D 2012
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 287
%N 1
%P 607-618
%@ 0021-9258
%X Nitrogen monoxide (NO) plays a role in the cytotoxic mechanisms of activated macrophages against tumor cells by inducing iron release. We showed that NO-mediated iron efflux from cells required glutathione (GSH) (Watts, R. N., and Richardson, D. R. (2001) J. Biol. Chem. 276, 4724-4732) and that the GSH-conjugate transporter, multidrug resistance-associated protein 1 (MRP1), mediates this release potentially as a dinitrosyl-dithiol iron complex (DNIC; Watts, R. N., Hawkins, C., Ponka, P., and Richardson, D. R. (2006) Proc. Natl. Acad. Sci. U.S.A. 103, 7670-7675). Recently, glutathione S-transferase P1-1 (GST P1-1) was shown to bind DNICs as dinitrosyl-diglutathionyl iron complexes. Considering this and that GSTs and MRP1 form an integrated detoxification unit with chemotherapeutics, we assessed whether these proteins coordinately regulate storage and transport of DNICs as long lived NO intermediates. Cells transfected with GSTP1 (but not GSTA1 or GSTM1) significantly decreased NO-mediated 59Fe release from cells. This NO-mediated 59Fe efflux and the effect of GST P1-1 on preventing this were observed with NO-generating agents and also in cells transfected with inducible nitric oxide synthase. Notably, 59Fe accumulated in cells within GST P1-1-containing fractions, indicating an alteration in intracellular 59Fe distribution. Furthermore, electron paramagnetic resonance studies showed that MCF7-VP cells transfected with GSTP1 contain significantly greater levels of a unique DNIC signal. These investigations indicate that GST P1-1 acts to sequester NO as DNICs, reducing their transport out of the cell by MRP1. Cell proliferation studies demonstrated the importance of the combined effect of GST P1-1 and MRP1 in protecting cells from the cytotoxic effects of NO. Thus, the DNIC storage function of GST P1-1 and ability of MRP1 to efflux DNICs are vital in protection against NO cytotoxicity.
%Z FOR Codes: 30406 60104


%0 Journal Article
%~ PubMed
%A Suryo Rahmanto, Yohan
%A Kalinowski, Danuta S
%A Lane, Darius Jr
%A Lok, Hiu Chuen
%A Richardson, Vera
%A Richardson, Des R
%T Nitrogen Monoxide (NO) Storage and Transport by Dinitrosyl-Dithiol-Iron Complexes: Long-Lived NO that is Trafficked by Interacting Proteins.
%B The Journal of Biological Chemistry
%D 2012
%C United States
%I American Society for Biochemistry and Molecular Bi
%V 287
%N 10
%P 6960-6968
%@ 1083-351X
%X 
%Z FOR Codes: 60104 60111


%0 Journal Article
%~ PubMed
%A Langley, David B
%A Shojaei, Maryam
%A Chan, Camilla
%A Lok, Hiu Chuen
%A Mackay, Joel P
%A Traut, Thomas W
%A Guss, J Mitchell
%A Christopherson, Richard I
%T Structure and Inhibition of Orotidine 5'-Monophosphate Decarboxylase from Plasmodium falciparum.
%B Biochemistry
%D 2009
%C United States
%I American Chemical Society
%V 48
%N 11
%P 2570
%@ 0006-2960
%X 
%Z FOR Codes: 60199 60199