ALTERED LOCALIZATION OF 73-KILODALTON HEAT-SHOCK PROTEIN IN RAT KIDNEYS WITH GENTAMICIN-INDUCED ACUTE TUBULAR INJURY

BACKGROUND: The constitutive 73-kilodalton heat-shock protein (HSP73) has been shown to have various essential functions in cells under both normal and stress conditions. In the present study, we observed seria l localizations of HSP73 in rat kidneys with gentamicin-induced acute tubular injury. EXPERIMENTAL DESIGN: Sprague-Dawley rats received gent amicin (80 mg/kg/day) for 14 days, and developed acute proximal tubula r injury. The intrarenal immunohistochemical distribution of HSP73 was examined by using a specific antibody against HSP73. In addition, HSP 73 content in both isotonic buffer- and detergent-extractable renal fr actions were measured by immunoblot analysis. RESULTS: After the genta micin exposure; HSP73 moved from the nucleus to the cytoplasm, and acc umulated in granules that were considered to be expressed within enlar ged lysosomes in the injured proximal tubular epithelial cells. These granules started to appear from 36 hours after the first gentamicin ex posure, enlarged in size until day 12, and gradually diminished after day 18. At day 27, the HSP73 localization pattern returned to that in the normal kidney. Moreover, significantly increased HSP73 protein ban ds were detected by immunoblot of detergent-extractable fractions from gentamicin-treated rat kidneys at from 36 hours to day 15 after the g entamicin exposure. CONCLUSIONS: Our findings suggest that HSP73 is ra pidly induced as an insoluble form in injured lysosomes of the proxima l tubular epithelial cells during gentamicin-induced acute tubular inj ury.