Komatsuda A, Wakui H, Ohtani H, Imai H, Miura A B, Itoh H
Third Department of Internal Medicine, Akita University School of Medicine, Akita City, Japan.
Pathol Int. 1999 Jun;49(6):513-8. doi: 10.1046/j.1440-1827.1999.00901.x.
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.
我们之前报道过，主要伴侣蛋白HSP73和HSP90在患有急性庆大霉素肾病的大鼠肾脏近端肾小管上皮细胞的溶酶体内蓄积。在本研究中，我们观察了HSP73和HSP90在患有急性溶酶体贮积症的大鼠肾脏中的连续定位情况。将Sprague-Dawley大鼠每日给予聚-D-谷氨酸（PDGA）（250 mg/kg），持续3天，从而引发近端肾小管上皮细胞的急性溶酶体贮积症。通过电子显微镜检查HSP73和HSP90的细胞内定位。我们还将结果与一种非伴侣蛋白——精氨琥珀酸合成酶的肾脏同工型进行了比较，该酶是近端肾小管上皮细胞中一种丰富的酶。在暴露于PDGA后，HSP73和HSP90在近端肾小管上皮细胞增大的溶酶体内蓄积。这些蓄积在首次给予PDGA后的第4天开始出现，大小持续增大直至第14天，并持续到第19天。精氨琥珀酸合成酶也在溶酶体内蓄积，但其在溶酶体中的蓄积程度小于HSP73和HSP90。我们的研究结果表明，在PDGA诱导的急性溶酶体贮积症过程中，HSP73和HSP90伴侣蛋白特异性地在近端肾小管上皮细胞的溶酶体内蓄积。
