The metallochemistry and molecular biology of iron converge in the study of ferritin structure and function. Ferritin is an iron binding protein whose regulation, once thought to be responsive only to changes in cellular iron content, has more recently been shown to be targeted by stress-induced stimuli, including cytokines, oxidants, and a range of xenobiotics. We now know that agents such as tumor necrosis factor, reactive oxygen species, and other stimuli trigger ferritin induction;ferritin, in turn, alters cellular iron homeostasis by sequestering reactive, """"""""low molecular weight"""""""" cellular iron. This in turn reduces susceptibility to subsequent stress. In this proposal we explore the hypothesis that ferritin regulation is instrumental in modulating the magnitude and character of the cellular response to injury and stress. We examine the unique contribution of ferritin to the phenotype of cells and tissues exposed to prooxidants and antioxidants. In our first Specific Aim, we explore the molecular mechanisms by which ferritin participates in the chemopreventive response to prooxidant xenobiotics. In our second Specific Aim, we explore potential pathways by which oxidative stress regulates ferritin in health and disease. In our third Specific Aim, we develop in vivo mouse models to test the relevance of our findings in the context of whole animals.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
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Metallobiochemistry Study Section (BMT)
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Wright, Daniel G
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Wake Forest University Health Sciences
Schools of Medicine
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Hatcher, Heather C; Tesfay, Lia; Torti, Suzy V et al. (2015) Cytoprotective Effect of Ferritin H in Renal Ischemia Reperfusion Injury. PLoS One 10:e0138505
Torti, Suzy V; Torti, Frank M (2013) Cellular iron metabolism in prognosis and therapy of breast cancer. Crit Rev Oncog 18:435-48
Chifman, J; Kniss, A; Neupane, P et al. (2012) The core control system of intracellular iron homeostasis: a mathematical model. J Theor Biol 300:91-9
Torti, Suzy V; Torti, Frank M (2011) Ironing out cancer. Cancer Res 71:1511-4
Miller, Lance D; Coffman, Lan G; Chou, Jeff W et al. (2011) An iron regulatory gene signature predicts outcome in breast cancer. Cancer Res 71:6728-37
Han, Jian; Seaman, William E; Di, Xiumin et al. (2011) Iron uptake mediated by binding of H-ferritin to the TIM-2 receptor in mouse cells. PLoS One 6:e23800
Li, Li; Fang, Celia J; Ryan, James C et al. (2010) Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. Proc Natl Acad Sci U S A 107:3505-10
Pinnix, Zandra K; Miller, Lance D; Wang, Wei et al. (2010) Ferroportin and iron regulation in breast cancer progression and prognosis. Sci Transl Med 2:43ra56
Wang, Wei; Knovich, Mary Ann; Coffman, Lan G et al. (2010) Serum ferritin: Past, present and future. Biochim Biophys Acta 1800:760-9
Wang, Wei; Di, Xiumin; Torti, Suzy V et al. (2010) Ferritin H induction by histone deacetylase inhibitors. Biochem Pharmacol 80:316-24

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