Quantitative imaging of metals in tissues

Ralle, Martina; Lutsenko, Svetlana

doi:10.1007/s10534-008-9200-5

Cited by 54 publications

(66 citation statements)

References 32 publications

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“…Paraffin has very low levels of trace element contamination and, thus, sections can be directly imaged without additional preparation (23). For some other trace elements, such deep tissue processing may lead to decreased detection and/or nonspecific signals (10).…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

Malinouski

Kehr

Finney

et al. 2012

Antioxidants & Redox Signaling

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Aim: Recent advances in quantitative methods and sensitive imaging techniques of trace elements provide opportunities to uncover and explain their biological roles. In particular, the distribution of selenium in tissues and cells under both physiological and pathological conditions remains unknown. In this work, we applied high-resolution synchrotron X-ray fluorescence microscopy (XFM) to map selenium distribution in mouse liver and kidney. Results: Liver showed a uniform selenium distribution that was dependent on selenocysteine tRNA [Ser]Sec and dietary selenium. In contrast, kidney selenium had both uniformly distributed and highly localized components, the latter visualized as thin circular structures surrounding proximal tubules. Other parts of the kidney, such as glomeruli and distal tubules, only manifested the uniformly distributed selenium pattern that co-localized with sulfur. We found that proximal tubule selenium localized to the basement membrane. It was preserved in Selenoprotein P knockout mice, but was completely eliminated in glutathione peroxidase 3 (GPx3) knockout mice, indicating that this selenium represented GPx3. We further imaged kidneys of another model organism, the naked mole rat, which showed a diminished uniformly distributed selenium pool, but preserved the circular proximal tubule signal. Innovation: We applied XFM to image selenium in mammalian tissues and identified a highly localized pool of this trace element at the basement membrane of kidneys that was associated with GPx3. Conclusion: XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution. Antioxid. Redox Signal. 16,[185][186][187][188][189][190][191][192]

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Section: Discussionmentioning

confidence: 99%

High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

Malinouski

Kehr

Finney

et al. 2012

Antioxidants & Redox Signaling

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“…X-ray fluorescence microscopy data were collected on beamline 2-ID-E at the Advanced Photon Source, Argonne National Laboratory (Argonne, IL). Samples were mounted onto lucite sample holders [made in-house (55)] and fit into a kinematic sample mount. Target regions were selected using a light microscope (Leica) equipped with a motorized x, y-stage (Ludl Electronic Products).…”

Section: Methodsmentioning

confidence: 99%

Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain

Öhrvik

Nose

Wood

et al. 2013

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

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113

141

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Significance Copper is essential for normal growth and development because it serves roles in catalysis, signaling, and structure. Cells acquire copper through the copper transporter 1 (Ctr1) protein, a copper transporter that localizes to the cell membrane and intracellular vesicles. Both copper and the anticancer drug cisplatin are imported by Ctr1 by virtue of an extracellular domain rich in metal-binding amino acids. In this report we demonstrate that a protein structurally related to Ctr1, called Ctr2, plays a role in the generation or stability of a truncated form of Ctr1 lacking a large portion of the extracellular domain. Retention of this domain in mice or cells lacking Ctr2 enhances copper and cisplatin uptake, thereby establishing Ctr2 as a regulator of Ctr1 function.

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“…Sulphur as a protein marker is present in the amino acids methionine and cysteine and is therefore distributed throughout the cell in all cellular proteins 13 . The Zn signal can be used as a proxy for the general size of the nucleus, as Zn content has been shown to be elevated in the nucleus 14,15 .…”

Section: Subcellular Elemental Quantificationmentioning

confidence: 99%

Alpha-Synuclein Regulates Neuronal Levels of Manganese and Calcium

Dučić¹,

Carboni

Lai

et al. 2015

ACS Chem. Neurosci.

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Manganese (Mn) may foster aggregation of alpha-synuclein (αSyn) contributing to the pathogenesis of PD. Here, we examined the influence of αSyn overexpression on distribution and oxidation states of Mn in frozen-hydrated primary midbrain neurons (PMNs) by synchrotron-based X-ray fluorescence (XRF) and X-ray absorption near edge structure spectroscopy (XANES). Overexpression of αSyn increased intracellular Mn levels, whereas levels of Ca, Zn, K, P, and S were significantly decreased. Mn oxidation states were not altered. A strong correlation between Cu-/Mn-levels as well as Fe-/Mn-levels was observed in αSyn-overexpressing cells. Subcellular resolution revealed a punctate or filament-like perinuclear and neuritic distribution of Mn, which resembled the expression of DMT1 and MnSOD. While overexpression of αSyn did not significantly alter the expression patterns of the most-expressed Mn transport proteins (DMT1, VGCC, Fpn1), it attenuated the Mn release from Mn-treated neurons. Thus, these data suggest that αSyn may act as an intracellular Mn store. In total, neurotoxicity in PD could be mediated via regulation of transition metal levels and the metal-binding capacity of αSyn, which could represent a promising therapeutic target for this neurodegenerative disorder.

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Quantitative imaging of metals in tissues

Cited by 54 publications

References 32 publications

High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

High-Resolution Imaging of Selenium in Kidneys: A Localized Selenium Pool Associated with Glutathione Peroxidase 3

Ctr2 regulates biogenesis of a cleaved form of mammalian Ctr1 metal transporter lacking the copper- and cisplatin-binding ecto-domain

Alpha-Synuclein Regulates Neuronal Levels of Manganese and Calcium

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