Synchrotron X-ray fluorescence studies of a bromine-labelled cyclic RGD peptide interacting with individual tumor cells

Sheridan, Erin J.; Austin, Christopher; Aitken, Jade B.; Vogt, Stefan; Jolliffe, Katrina A.; Harris, Hugh H.; Rendina, Louis M.

doi:10.1107/s0909049513001647

Cited by 11 publications

(7 citation statements)

References 53 publications

(47 reference statements)

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“…The intra‐cellular localization of Co 2+ to nuclear and perinuclear sites in osteoblasts is consistent with its known interactions with genomic DNA and nuclear proteins associated with DNA repair . Our finding that Co 2+ was also distributed throughout the cell body is in keeping with the distribution of other divalent cations, such as Ca 2+ and Zn 2+ that have established plasma membrane channels and transporters, and may suggest use of similar transport machinery. In support of this, our calcein quenching studies suggest that the P2X7R contributes to this transport.…”

Section: Discussionsupporting

confidence: 82%

Understanding the tissue effects of tribo‐corrosion: Uptake, distribution, and speciation of cobalt and chromium in human bone cells

Shah

Quinn

Gartland

et al. 2014

Journal Orthopaedic Research

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Cobalt and chromium species are released in the local tissues as a result of tribo-corrosion, and affect bone cell survival and function. However we have little understanding of the mechanisms of cellular entry, intracellular distribution, and speciation of the metals that result in impaired bone health. Here we used synchrotron based X-ray fluorescence (XRF), X-ray absorption spectroscopy (XAS), and fluorescent-probing approaches of candidate receptors P2X7R and divalent metal transporter-1 (DMT-1), to better understand the entry, intra-cellular distribution and speciation of cobalt (Co) and chromium (Cr) in human osteoblasts and primary human osteoclasts. We found that both Co and Cr were most highly localized at nuclear and perinuclear sites in osteoblasts, suggesting uptake through cell membrane transporters, and supported by a finding that P2X7 receptor blockade reduced cellular entry of Co. In contrast, metal species were present at discrete sites corresponding to the basolateral membrane in osteoclasts, suggesting cell entry by endocytosis and trafficking through a functional secretory domain. An intracellular reduction of Cr 6þ to Cr 3þ was the only redox change observed in cells treated with Co 2-4We, and others, have previously shown that these concentrations of Co and Cr affect bone cell survival and function in-vitro, 5-7 and associate with systemically measurable effects on bone mass and bone turnover in patients. 8 In order to understand the adverse effects of metal debris exposure on bone health and how these effects may be mitigated, it is necessary to understand how metal enters the relevant cell populations, and their intracellular distribution and speciation characteristics. In this study we have used microfocus X-ray spectroscopy, an analytical technique that uses highenergy X-ray beams derived by synchrotron radiation, to determine the chemical form and oxidation state of an element in microscopic samples.9-11 Specifically, we have used Microfocus X-ray fluorescence (m-XRF) to measure the elemental distribution and micro-X-ray absorption near-edge structure (m-XANES) to characterize the chemical form of the metals in human bone cells.We also investigated the role of two candidate metal transporters, the P2X7 receptor (P2X7R) and the divalent metal transport-1 (DMT-1), in the cellular entry of Co and Cr in human bone cells. The P2X7R is expressed in both human osteoblasts and osteoclasts and plays an important role in bone homeostasis. 12,13The DMT-1 is a ubiquitously expressed transporter of ferrous iron and a broad range of other divalent cations, including Co 2þ

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Section: Discussionsupporting

confidence: 82%

Understanding the tissue effects of tribo‐corrosion: Uptake, distribution, and speciation of cobalt and chromium in human bone cells

Shah

Quinn

Gartland

et al. 2014

Journal Orthopaedic Research

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“…1 , 2 , S1 ) represent the natural distributions in living MIN6 cells. To evaluate whether our results are biologically realistic, we used the elemental spatial densities per pixel as a rough comparison with other SXRF studies 25 27 37 38 39 40 41 . These studies were conducted at different synchrotrons, used a variety of cell types, sample preparations and experimental conditions (all imaged cells at lower spatial resolutions than presented here).…”

Section: Resultsmentioning

confidence: 99%

Imaging trace element distributions in single organelles and subcellular features

Kashiv

Austin

Lai

et al. 2016

Sci Rep

Self Cite

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The distributions of chemical elements within cells are of prime importance in a wide range of basic and applied biochemical research. An example is the role of the subcellular Zn distribution in Zn homeostasis in insulin producing pancreatic beta cells and the development of type 2 diabetes mellitus. We combined transmission electron microscopy with micro- and nano-synchrotron X-ray fluorescence to image unequivocally for the first time, to the best of our knowledge, the natural elemental distributions, including those of trace elements, in single organelles and other subcellular features. Detected elements include Cl, K, Ca, Co, Ni, Cu, Zn and Cd (which some cells were supplemented with). Cell samples were prepared by a technique that minimally affects the natural elemental concentrations and distributions, and without using fluorescent indicators. It could likely be applied to all cell types and provide new biochemical insights at the single organelle level not available from organelle population level studies.

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“…Typical approaches use metal-labeled drugs or other tagged molecules that are anticipated to be preferentially taken up by the cancerous cells, often by dint of some facet related to the cancerous cell's growth or nutrient requirements; the targeted location within the tumor or tumor cells can be identified through tracking the tagging element. 222 XFI has been used to identify the localization of Gd and Pt within treated tumor cells, 223 where incorporation of these heavy elements is ultimately anticipated to enhance neutron capture therapy and synchrotron stereotactic radiotherapy treatments. XFI tomography has been used to map the platinum distribution in DLD-1 colorectal cancer cell spheroids that had been exposed to platinum-containing anticancer drugs.…”

Section: Pharmacological Applicationsmentioning

confidence: 99%

Elemental and Chemically Specific X-ray Fluorescence Imaging of Biological Systems

et al. 2014

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Synchrotron X-ray fluorescence studies of a bromine-labelled cyclic RGD peptide interacting with individual tumor cells

Cited by 11 publications

References 53 publications

Understanding the tissue effects of tribo‐corrosion: Uptake, distribution, and speciation of cobalt and chromium in human bone cells

Understanding the tissue effects of tribo‐corrosion: Uptake, distribution, and speciation of cobalt and chromium in human bone cells

Imaging trace element distributions in single organelles and subcellular features

Elemental and Chemically Specific X-ray Fluorescence Imaging of Biological Systems

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