Activity-based sensing fluorescent probes for iron in biological systems

Aron, Allegra T.; Reeves, Audrey G.; Chang, Christopher J.

doi:10.1016/j.cbpa.2017.12.010

Cited by 94 publications

(57 citation statements)

References 62 publications

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“…This study reviews our group’s development of fluorescent probes for selective detection and live imaging of the subcellular labile Fe(II) ions by utilizing the N -oxide chemistry. In addition to our N -oxide-based fluorescent probes, the Fe(II)-selective fluorescent probes that were based on endoperoxide chemistry [ 2 , 3 , 31 ] have been reported by other group, who have also provided a discussion regarding their biological applications [ 4 ]. Iron is essential to perform homeostatic regulation; a surplus or deficiency of iron can cause several serious diseases.…”

Section: Discussionmentioning

confidence: 99%

Development of Chemical Tools for Imaging of Fe(II) Ions in Living Cells: A Review

Hirayama

2018

Acta Histochemica et Cytochemica

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Intracellular labile iron is an iron species which is not or weakly bound to proteins and depicts an important effect on homeostatic regulation in cells. An excess or deficiency of iron can cause oxidative damage to key cellular biomolecules. The behavior and concentrations of labile iron are difficult to monitor, but the specific redox state of the Fe ions is relevant to the physiological and pathological properties that we would like to study. We have developed a series of turn-on type fluorescent probes that are highly selective to the labile Fe(II) ions, and we have tested their applications to cellular level imaging. These probes are based on N-oxide chemistry with a range of fluorophores that depict optimal performance for specific applications. Herein, I review the recent progress of our research and discuss prospects for future work to understand the relation between intracellular ion and oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Development of Chemical Tools for Imaging of Fe(II) Ions in Living Cells: A Review

Hirayama

2018

Acta Histochemica et Cytochemica

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“…S3a). We therefore utilized two first generation activity-based 'turn-on' probes that are capable of selectively detecting Fe 2+ over other biologically relevant metals including Mn (Aron et al 2018). RhoNox-1 interacts with Fe 2+ resulting in the release of fluorescent rhodamine and was recently reported to selectively detect endogenous changes in LIP of lung carcinoma cells (Niwa et al 2014;Adachi et al 2016), while IP-1 relies on an oxygen-dependent, three-component sensing mechanism to detect Fe 2+ (Au-Yeung et al 2013).…”

Section: Manganese-dependent Transcriptional Response Of App and H-fementioning

confidence: 99%

Manganese causes neurotoxic iron accumulation via translational repression of amyloid precursor protein and H‐Ferritin

Venkataramani

Doeppner

Willkommen

et al. 2018

Journal of Neurochemistry

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For more than 150 years, it is known that occupational overexposure of manganese (Mn) causes movement disorders resembling Parkinson's disease (PD) and PD-like syndromes. However, the mechanisms of Mn toxicity are still poorly understood. Here, we demonstrate that Mn dose- and time-dependently blocks the protein translation of amyloid precursor protein (APP) and heavy-chain Ferritin (H-Ferritin), both iron homeostatic proteins with neuroprotective features. APP and H-Ferritin are post-transcriptionally regulated by iron responsive proteins, which bind to homologous iron responsive elements (IREs) located in the 5'-untranslated regions (5'-UTRs) within their mRNA transcripts. Using reporter assays, we demonstrate that Mn exposure repressed the 5'-UTR-activity of APP and H-Ferritin, presumably via increased iron responsive proteins-iron responsive elements binding, ultimately blocking their protein translation. Using two specific Fe -specific probes (RhoNox-1 and IP-1) and ion chromatography inductively coupled plasma mass spectrometry (IC-ICP-MS), we show that loss of the protective axis of APP and H-Ferritin resulted in unchecked accumulation of redox-active ferrous iron (Fe ) fueling neurotoxic oxidative stress. Enforced APP expression partially attenuated Mn-induced generation of cellular and lipid reactive oxygen species and neurotoxicity. Lastly, we could validate the Mn-mediated suppression of APP and H-Ferritin in two rodent in vivo models (C57BL6/N mice and RjHan:SD rats) mimicking acute and chronic Mn exposure. Together, these results suggest that Mn-induced neurotoxicity is partly attributable to the translational inhibition of APP and H-Ferritin resulting in impaired iron metabolism and exacerbated neurotoxic oxidative stress. Open Data: Materials are available on https://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/.

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“…This work complements our recent efforts to develop activity-based uorescent probes for iron(II). [47][48][49][50][51][52] The polymer PAF-1-ET was synthesized in three steps, starting with the synthesis of parent PAF-1 and PAF-1-CH 2 Cl (see the ESI †) 40 followed by treatment of the latter with 2-(methylthio)ethan-1-ol to yield PAF-1-ET (Fig. 1a).…”

Section: Synthesis and Characterizationmentioning

confidence: 99%

Iron Detection and Remediation with a Functionalized Porous Polymer Applied to Environmental Water Samples

Lee¹,

Uliana²,

Taylor³

et al. 2019

Preprint

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<div> <p>Iron is one of the most abundant elements in the environment and in the human body. As an essential nutrient, iron homeostasis is tightly regulated, and iron dysregulation is implicated in numerous pathologies, including neuro-degenerative diseases, atherosclerosis, and diabetes. Endogenous iron pool concentrations are directly linked to iron ion uptake from environmental sources such as drinking water, providing motivation for developing new technologies for assessing iron(II) and iron(III) levels in water. However, conventional methods for measuring aqueous iron pools remain laborious and costly and often require sophisticated equipment and/or additional processing steps to remove the iron ions from the original environmental source. We now report a simplified and accurate chemical platform for capturing and quantifying the iron present in aqueous samples through use of a post-synthetically modified porous aromatic framework (PAF). The ether/thioether-functionalized network polymer, PAF-1-ET, exhibits high selectivity for the uptake of iron(II) and iron(III) over other physiologically and environmentally relevant metal ions. Mössbauer spectroscopy, XANES, and EXAFS measurements provide evidence to support iron(III) coordination to oxygen-based ligands within the material. The polymer is further successfully employed to adsorb and remove iron ions from groundwater, including field sources in West Bengal, India. Combined with an 8-hydroxyquinoline colorimetric indicator, PAF-1-ET enables the simple and direct determination of the iron(II) and iron(III) ion concentrations in these samples, providing a starting point for the design and use of molecularly-functionalized porous materials for potential dual detection and remediation applications.</p></div>

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Activity-based sensing fluorescent probes for iron in biological systems

Cited by 94 publications

References 62 publications

Development of Chemical Tools for Imaging of Fe(II) Ions in Living Cells: A Review

Development of Chemical Tools for Imaging of Fe(II) Ions in Living Cells: A Review

Manganese causes neurotoxic iron accumulation via translational repression of amyloid precursor protein and H‐Ferritin

Iron Detection and Remediation with a Functionalized Porous Polymer Applied to Environmental Water Samples

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