title: Intracellular localization of HSP73 and HSP90 in rat kidneys with acute lysosomal thesaurismosis.
abstract: We previously reported that HSP73 and HSP90, major chaperone proteins, accumulated within lysosomes of proximal tubular epithelial cells in rat kidneys with acute gentamicin nephropathy. In this study, we observed serial localization of HSP73 and HSP90 in rat kidneys with acute lysosomal thesaurismosis. Sprague-Dawley rats received poly-D-glutamic acid (PDGA) (250 mg/kg per day) for 3 days, and developed acute lysosomal thesaurismosis of proximal tubular epithelial cells. The intracellular localization of HSP73 and HSP90 was examined by electron microscopy. We also compared the results with those of a non-chaperone protein, a renal isoform of argininosuccinate synthetase, which is an abundant enzyme in proximal tubular epithelial cells. After the PDGA exposure, HSP73 and HSP90 accumulated within enlarged lysosomes of proximal tubular epithelial cells. These accumulations started to appear from day 4 after the first PDGA administration, enlarged in size until day 14, and continued until day 19. Argininosuccinate synthetase also accumulated within the lysosomes, but the magnitude of this lysosomal accumulation was less than those of HSP73 and HSP90. Our findings demonstrated that HSP73 and HSP90 chaperone proteins specifically accumulated within lysosomes of proximal tubular epithelial cells during the course of PDGA-induced acute lysosomal thesaurismosis.
authors.affiliation: Third Department of Internal Medicine, Akita University School of Medicine, Akita City, Japan. komatsud@med.akita-u.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Komatsuda
authors.forename: H
authors.initials: H
authors.lastname: Wakui
authors.forename: H
authors.initials: H
authors.lastname: Ohtani
authors.forename: H
authors.initials: H
authors.lastname: Imai
authors.forename: A B
authors.initials: AB
authors.lastname: Miura
authors.forename: H
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000118:Acetylglucosaminidase / Q000652:urine; D000208:Acute Disease; D000818:Animals; D001774:Blood Chemical Analysis; D002352:Carrier Proteins / Q000378:metabolism*; D002401:Cathepsin B / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008659:Metabolic Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011099:Polyglutamic Acid / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine
chemical_list: D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C494373:Hspa8 protein, rat; D011099:Polyglutamic Acid; D000118:Acetylglucosaminidase; D002401:Cathepsin B