title: High-resolution imaging of selenium in kidneys: a localized selenium pool associated with glutathione peroxidase 3.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  XFM allowed us to define and explain the tissue topography of selenium in mammalian kidneys at submicron resolution.
authors.affiliation: Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mikalai
authors.initials: M
authors.lastname: Malinouski
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kehr
authors.forename: Lydia
authors.initials: L
authors.lastname: Finney
authors.forename: Stefan
authors.initials: S
authors.lastname: Vogt
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Carlson
authors.forename: Javier
authors.initials: J
authors.lastname: Seravalli
authors.forename: Richard
authors.initials: R
authors.lastname: Jin
authors.forename: Diane E
authors.initials: DE
authors.lastname: Handy
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Park
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000201:enzymology / Q000378:metabolism; D004577:Electron Probe Microanalysis; D055786:Gene Knockout Techniques; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000201:enzymology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019577:Mole Rats; D012346:RNA, Transfer, Amino Acyl / Q000235:genetics; D012643:Selenium / Q000378:metabolism*; D051149:Selenoprotein P / Q000235:genetics; D013052:Spectrometry, X-Ray Emission
chemical_list: D012346:RNA, Transfer, Amino Acyl; D051149:Selenoprotein P; C112705:selenocysteinyl-tRNA; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase; D012643:Selenium