title: Extracellular glutathione peroxidase (Gpx3) binds specifically to basement membranes of mouse renal cortex tubule cells.
abstract: Glutathione peroxidase-3 (Gpx3), also known as plasma or extracellular glutathione peroxidase, is a selenoprotein secreted primarily by kidney proximal convoluted tubule cells. In this study Gpx3(-/-) mice have been produced and immunocytochemical techniques have been developed to investigate Gpx3 metabolism. Gpx3(-/-) mice maintained the same whole-body content and urinary excretion of selenium as did Gpx3(+/+) mice. They tolerated selenium deficiency without observable ill effects. The simultaneous knockout of Gpx3 and selenoprotein P revealed that these two selenoproteins account for >97% of plasma selenium. Immunocytochemistry experiments demonstrated that Gpx3 binds selectively, both in vivo and in vitro, to basement membranes of renal cortical proximal and distal convoluted tubules. Based on calculations using selenium content, the kidney pool of Gpx3 is over twice as large as the plasma pool. These data indicate that Gpx3 does not serve in the regulation of selenium metabolism. The specific binding of a large pool of Gpx3 to basement membranes in the kidney cortex strongly suggests a need for glutathione peroxidase activity in the cortical peritubular space.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
authors.forename: Gary E
authors.initials: GE
authors.lastname: Olson
authors.forename: John C
authors.initials: JC
authors.lastname: Whitin
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Hill
authors.forename: Virginia P
authors.initials: VP
authors.lastname: Winfrey
authors.forename: Amy K
authors.initials: AK
authors.lastname: Motley
authors.forename: Lori M
authors.initials: LM
authors.lastname: Austin
authors.forename: Jacqualyn
authors.initials: J
authors.lastname: Deal
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Cohen
authors.forename: Raymond F
authors.initials: RF
authors.lastname: Burk
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D005260:Female; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D007672:Kidney Cortex / Q000166:cytology* / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D012643:Selenium / Q000378:metabolism; D051149:Selenoprotein P / Q000172:deficiency / Q000235:genetics / Q000378:metabolism
chemical_list: D051149:Selenoprotein P; C116888:Gpx3 protein, mouse; D005979:Glutathione Peroxidase; D012643:Selenium