Age-dependent and gender-specific changes in mouse tissue iron by strain

Hahn, Paul; Song, Ying; Ying, Gui‐Shuang; He, Xuming; Beard, John L.; Dunaief, Joshua L.

doi:10.1016/j.exger.2009.06.006

Cited by 79 publications

(67 citation statements)

References 43 publications

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“…S10B). The results suggest that females may have higher resting levels of LIPs compared with males, an interesting but complex observation that merits further investigation (61,62).…”

Section: Resultsmentioning

confidence: 98%

In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection

Aron

Heffern

Lonergan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

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Iron is an essential metal for all organisms, yet disruption of its homeostasis, particularly in labile forms that can contribute to oxidative stress, is connected to diseases ranging from infection to cancer to neurodegeneration. Iron deficiency is also among the most common nutritional deficiencies worldwide. To advance studies of iron in healthy and disease states, we now report the synthesis and characterization of iron-caged luciferin-1 (ICL-1), a bioluminescent probe that enables longitudinal monitoring of labile iron pools (LIPs) in living animals. ICL-1 utilizes a bioinspired endoperoxide trigger to release D-aminoluciferin for selective reactivity-based detection of Fe 2+ with metal and oxidation state specificity. The probe can detect physiological changes in labile Fe 2+ levels in live cells and mice experiencing iron deficiency or overload. Application of ICL-1 in a model of systemic bacterial infection reveals increased iron accumulation in infected tissues that accompany transcriptional changes consistent with elevations in both iron acquisition and retention. The ability to assess iron status in living animals provides a powerful technology for studying the contributions of iron metabolism to physiology and pathology.labile iron | molecular imaging | luciferin | metal homeostasis | infectious disease I ron is an essential mineral for nearly every form of life, owing in large part to its ability to cycle between different oxidation states for processes such as nucleotide synthesis, oxygen transport, and respiration (1, 2). At the same time, the potent redox activity of iron is potentially toxic, particularly in unregulated labile forms that can trigger aberrant production of reactive oxygen species via Fenton chemistry (3). Indeed, iron deficiency remains one of the most common nutritional deficiencies in the world (4), and aberrant iron levels have been linked to various ailments, including cancer (5-7), cardiovascular (8), and neurodegenerative (9) disorders, as well as aging (10). The situation is especially complex in infectious diseases, where the requirement for iron by both host organism and invading pathogen leads to an intricate chemical tug-of-war for this metal nutrient during various stages of the immune response (11,12).The foregoing examples provide motivation for developing technologies to monitor biological iron status, with particular interest in methods to achieve in vivo iron imaging in live animal models that go beyond current state-of-the-art assays that are limited primarily to cell culture specimens. In this regard, detection of iron with both metal and oxidation state specificity is of central importance, because while iron is stored primarily in the ferric oxidation state, a ferrous iron pool loosely bound to cellular ligands, defined as the labile iron pool (LIP), exists at the center of highly regulated networks that control iron acquisition, trafficking, and excretion. Indeed, as a weak binder on the Irving-Williams stability series (13), Fe 2+ provides a challenge for d...

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“…S10B). The results suggest that females may have higher resting levels of LIPs compared with males, an interesting but complex observation that merits further investigation (61,62).…”

Section: Resultsmentioning

confidence: 98%

In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection

Aron

Heffern

Lonergan

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

113

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“…In fact, oxidant-mediated damages of macromolecules disturb redox-sensitive signaling (Altamura and Muckenthaler 2009) and cause mitochondrial dysfunction (Lin and Beal 2006) as well as brain cell death (Mattson 2006). Additionally, accumulation of metal ions, especially iron, has been observed in the aged central nervous system in humans (Aquino et al 2009) and animal models (Hahn et al 2009) as well as in disorders such as Alzheimer’s disease (Honda et al 2005;Altamura and Muckenthaler 2009), Huntington’s disease (Simmons et al 2007;Bartzokis et al 2007), Parkinson’s disease (Lee and Andersen 2010) and Friedreich’s ataxia (Pandolfo and Pastore 2009). …”

Section: Iron Crisis and Mitochondrial Decaymentioning

confidence: 99%

The emerging role of iron dyshomeostasis in the mitochondrial decay of aging

Marzetti

Seo

et al. 2010

Mechanisms of Ageing and Development

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“…11 These data, however, were pooled from mice of various ages (4, 8 and 16 weeks). Given that hepatic iron concentrations vary with age, 52 the pooling of mice at different ages could obscure significant differences between groups. Indeed, recent comparisons of mice of the same age (4 weeks) revealed that hepatic iron concentrations were 40% lower (P<0.001) in Zip14 knockout mice (n=8) than in controls (n=6) (unpublished observations, S. Jenkitkasemwong and M. Knutson).…”

mentioning

confidence: 99%

ZIP14 and DMT1 in the liver, pancreas, and heart are differentially regulated by iron deficiency and overload: implications for tissue iron uptake in iron-related disorders

et al. 2013

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ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n . Collectively, these data suggest that ZIP14 may not only function during iron overload to take up NTBI, but also under normal or iron-deficient conditions when cells take up iron via endocytosis of transferrin. The aim of the present study was to determine how iron deficiency and overload affect the expression of ZIP14 and DMT1 in the liver, pancreas, and heart. The localization of ZIP14 in liver and pancreas was also determined. Knowledge of where ZIP14 is expressed in these organs and how ZIP14 and DMT1 are regulated in vivo by iron will help us to better assess the contribution of these transporters to tissue iron uptake. Design and Methods Animals, diets, and non-heme iron determinationRats were made iron-deficient, iron-adequate, or iron-loaded as described previously. 10 Briefly, weanling (21-day-old) male Sprague-Dawley rats were fed modified AIN-93G purified diets containing iron at 10 ppm (iron deficient, FeD), 50 ppm (iron adequate, FeA), or 18,916 ppm (iron overload, FeO) for 3 weeks. Male Zip14 (Slc39a14) knockout and wild-type control mice maintained on the 129+Ter/SvJcl x C57BL/6 background 11 were analyzed at 6 weeks of age. Male and female hypotransferrinemic (hpx) mice and wild-type controls maintained on the BALB/cJ background were analyzed at 16 weeks of age. Homozygous hpx mice were given a weekly intraperitoneal injection of human apo-transferrin (0.6-1.8 mg) (EMD Chemicals). All mice consumed a commercial rodent diet containing 240 ppm iron (Teklad 7912, Harlan Laboratories). At the end of the studies, animals were anesthetized with vaporized isoflurane and sacrificed by exsanguination via the descending aorta. Tissues were harvested, immediately frozen in liquid nitrogen, and stored at -80°C until use. Animal protocols were approved by the University of Florida Institutional Animal Care and Use Committee. Tissue non-heme iron concentrations were determined colorimetrically after acid digestion of tissues. 12 Generation of ZIP14 antibodyRabbit anti-ZIP14 antiserum was generated against peptide ENEQTEEGKPSAIEVC corresponding to amino acids 138-153 of rat ZIP14. Antibodies specific to the ZIP14 peptide immunogen were affinity purified by using a peptide-agarose column of SulfoLink coupling gel (Pierce). Sample preparation and western blot analysisThe preparation of samples and western blot analysis are described in the Online Supplementary Design and Methods. Transfection, immunoprecipitation, and enzymatic deglycosylationEffectene reagent (Qiagen) was used to transiently transfect HEK 293T cells with either empty pCMV-Sport2 (control) or pCMV-Sport6 containing rat ZIP14 cDNA. To immunoprecipitate ZIP14, anti-ZIP14 antibody (400 mg) was covalently linked to AminoLink Plus Coupling Resin (Thermo Scientific) and added to a Pierce Spin Column according to the manufacturer's protocol. Immunoprecipitations were performed using the CoImmunoprecipitation Kit (Pierce) according to the manufacturer's instructions. To assess protein glycosylati...

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Age-dependent and gender-specific changes in mouse tissue iron by strain

Cited by 79 publications

References 43 publications

In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection

In vivo bioluminescence imaging of labile iron accumulation in a murine model of Acinetobacter baumannii infection

The emerging role of iron dyshomeostasis in the mitochondrial decay of aging

ZIP14 and DMT1 in the liver, pancreas, and heart are differentially regulated by iron deficiency and overload: implications for tissue iron uptake in iron-related disorders

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