On the nature of the Cu-rich aggregates in brain astrocytes
Fulfilling a bevy of biological roles, copper is an essential metal for healthy brain function. Cu dyshomeostasis has been demonstrated to be involved in some neurological conditions including Menkes and Alzheimer's diseases. We have previously reported localized Cu-rich aggregates in astrocyte...
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doaj-a3591335fc2a433fbb8e48a9484017252020-11-25T02:52:09ZengElsevierRedox Biology2213-23172017-04-0111231239On the nature of the Cu-rich aggregates in brain astrocytesBrendan Sullivan0Gregory Robison1Jenna Osborn2Martin Kay3Peter Thompson4Katherine Davis5Taisiya Zakharova6Olga Antipova7Yulia Pushkar8Department of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United StatesDepartment of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United StatesDepartment of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United StatesDepartment of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United StatesDepartment of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United StatesDepartment of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United StatesDepartment of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United StatesBioCAT, Advanced Photon Source, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, IL 60439, United States; XSD, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, IL 60439, United StatesDepartment of Physics and Astronomy, Purdue University, 525 Northwestern Ave., West Lafayette, IN 47907, United States; Corresponding author.Fulfilling a bevy of biological roles, copper is an essential metal for healthy brain function. Cu dyshomeostasis has been demonstrated to be involved in some neurological conditions including Menkes and Alzheimer's diseases. We have previously reported localized Cu-rich aggregates in astrocytes of the subventricular zone (SVZ) in rodent brains with Cu concentrations in the hundreds of millimolar. Metallothionein, a cysteine-rich protein critical to metal homeostasis and known to participate in a variety of neuroprotective and neuroregenerative processes, was proposed as a binding protein. Here, we present an analysis of metallothionein(1,2) knockout (MTKO) mice and age-matched controls using X-ray fluorescence microscopy. In large structures such as the corpus callosum, cortex, and striatum, there is no significant difference in Cu, Fe, or Zn concentrations in MTKO mice compared to age-matched controls. In the astrocyte-rich subventricular zone where Cu-rich aggregates reside, approximately 1/3 as many Cu-rich aggregates persist in MTKO mice resulting in a decrease in periventricular Cu concentration. Aggregates in both wild-type and MTKO mice show XANES spectra characteristic of CuxSy multimetallic clusters and have similar [S]/[Cu] ratios. Consistent with assignment as a CuxSy multimetallic cluster, the astrocyte-rich SVZ of both MTKO and wild-type mice exhibit autofluorescent bodies, though MTKO mice exhibit fewer. Furthermore, XRF imaging of Au-labeled lysosomes and ubiquitin demonstrates a lack of co-localization with Cu-rich aggregates suggesting they are not involved in a degradation pathway. Overall, these data suggest that Cu in aggregates is bound by either metallothionein-3 or a yet unknown protein similar to metallothionein. Keywords: X-ray fluorescence microscopy, Subventricular zone, Cu, Metallothioneinhttp://www.sciencedirect.com/science/article/pii/S2213231716301173 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Brendan Sullivan Gregory Robison Jenna Osborn Martin Kay Peter Thompson Katherine Davis Taisiya Zakharova Olga Antipova Yulia Pushkar |
spellingShingle |
Brendan Sullivan Gregory Robison Jenna Osborn Martin Kay Peter Thompson Katherine Davis Taisiya Zakharova Olga Antipova Yulia Pushkar On the nature of the Cu-rich aggregates in brain astrocytes Redox Biology |
author_facet |
Brendan Sullivan Gregory Robison Jenna Osborn Martin Kay Peter Thompson Katherine Davis Taisiya Zakharova Olga Antipova Yulia Pushkar |
author_sort |
Brendan Sullivan |
title |
On the nature of the Cu-rich aggregates in brain astrocytes |
title_short |
On the nature of the Cu-rich aggregates in brain astrocytes |
title_full |
On the nature of the Cu-rich aggregates in brain astrocytes |
title_fullStr |
On the nature of the Cu-rich aggregates in brain astrocytes |
title_full_unstemmed |
On the nature of the Cu-rich aggregates in brain astrocytes |
title_sort |
on the nature of the cu-rich aggregates in brain astrocytes |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2017-04-01 |
description |
Fulfilling a bevy of biological roles, copper is an essential metal for healthy brain function. Cu dyshomeostasis has been demonstrated to be involved in some neurological conditions including Menkes and Alzheimer's diseases. We have previously reported localized Cu-rich aggregates in astrocytes of the subventricular zone (SVZ) in rodent brains with Cu concentrations in the hundreds of millimolar. Metallothionein, a cysteine-rich protein critical to metal homeostasis and known to participate in a variety of neuroprotective and neuroregenerative processes, was proposed as a binding protein. Here, we present an analysis of metallothionein(1,2) knockout (MTKO) mice and age-matched controls using X-ray fluorescence microscopy. In large structures such as the corpus callosum, cortex, and striatum, there is no significant difference in Cu, Fe, or Zn concentrations in MTKO mice compared to age-matched controls. In the astrocyte-rich subventricular zone where Cu-rich aggregates reside, approximately 1/3 as many Cu-rich aggregates persist in MTKO mice resulting in a decrease in periventricular Cu concentration. Aggregates in both wild-type and MTKO mice show XANES spectra characteristic of CuxSy multimetallic clusters and have similar [S]/[Cu] ratios. Consistent with assignment as a CuxSy multimetallic cluster, the astrocyte-rich SVZ of both MTKO and wild-type mice exhibit autofluorescent bodies, though MTKO mice exhibit fewer. Furthermore, XRF imaging of Au-labeled lysosomes and ubiquitin demonstrates a lack of co-localization with Cu-rich aggregates suggesting they are not involved in a degradation pathway. Overall, these data suggest that Cu in aggregates is bound by either metallothionein-3 or a yet unknown protein similar to metallothionein. Keywords: X-ray fluorescence microscopy, Subventricular zone, Cu, Metallothionein |
url |
http://www.sciencedirect.com/science/article/pii/S2213231716301173 |
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