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 serial localizations of HSP73 in rat kidneys with gentamicin-induced acute tubular injury.


METHODS
Sprague-Dawley rats received gentamicin (80 mg/kg/day) for 14 days, and developed acute proximal tubular injury. The intrarenal immunohistochemical distribution of HSP73 was examined by using a specific antibody against HSP73. In addition, HSP73 content in both isotonic buffer- and detergent-extractable renal fractions were measured by immunoblot analysis.


RESULTS
After the gentamicin exposure, HSP73 moved from the nucleus to the cytoplasm, and accumulated in granules that were considered to be expressed within enlarged lysosomes in the injured proximal tubular epithelial cells. These granules started to appear from 36 hours after the first gentamicin exposure, 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 bands were detected by immunoblot of detergent-extractable fractions from gentamicin-treated rat kidneys at from 36 hours to day 15 after the gentamicin exposure.


CONCLUSIONS
Our findings suggest that HSP73 is rapidly induced as an insoluble form in injured lysosomes of the proximal tubular epithelial cells during gentamicin-induced acute tubular injury.
Third Department of Internal Medicine, Akita University School of Medicine, Japan.
A
A
Komatsuda
H
H
Wakui
K
K
Satoh
T
T
Yasuda
H
H
Imai
Y
Y
Nakamoto
A B
AB
Miura
H
H
Itoh
Y
Y
Tashima
D000818:Animals; D004195:Disease Models, Animal; D005839:Gentamicins; D006360:Heat-Shock Proteins / Q000032:analysis*; D007683:Kidney Tubular Necrosis, Acute / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000652:urine; D008247:Lysosomes / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005839:Gentamicins; D006360:Heat-Shock Proteins