Intracellular localization of HSP73 and HSP90 in rat kidneys with acute lysosomal thesaurismosis

We previously reported that HSP73 and HSP90, major chaperone proteins, accu mulated within lysosomes of proximal tubular epithelial cells in rat kidney s with acute gentamicin nephropathy. In this study, we observed serial loca lization of HSP73 and HSP90 in rat kidneys with acute lysosomal thesaurismo sis. Sprague-Dawley rats received poly-D-glutamic acid (PDGA) (250 mg/kg pe r day) for 3 days, and developed acute lysosomal thesaurismosis of proximal tubular epithelial cells. The intracellular localization of HSP73 and HSP9 0 was examined by electron microscopy. We also compared the results with th ose of a non-chaperone protein, a renal isoform of argininosuccinate synthe tase, which is an abundant enzyme in proximal tubular epithelial cells. Aft er the PDGA exposure, HSP73 and HSP90 accumulated within enlarged lysosomes of proximal tubular epithelial cells. These accumulations started to appea r from day 4 after the first PDGA administration, enlarged in size until da y 14, and continued until day 19. Argininosuccinate synthetase also accumul ated within the lysosomes, but the magnitude of this lysosomal accumulation was less than those of HSP73 and HSP90. Our findings demonstrated that HSP 73 and HSP90 chaperone proteins specifically accumulated within lysosomes o f proximal tubular epithelial cells during the course of PDGA-induced acute lysosomal thesaurismosis.