Increased heat shock protein-70 in unilateral ureteral obstruction in rats

Our previous studies noted the oxidative stress of unilateral ureteral obst ruction (UUO). Now, we seek to explore whether UUO affects the intrinsic ce llular antioxidants and triggers heat shock protein (HSP-70) and whether th ese are still highly expressed after reversal of the UUO (R-UUO). In additi on, we designed the experiment to determine whether this expression of HSP- 70 is a localized or a generalized response. Male Sprague-Dawley rats (125- 150 g) were randomly assigned to sham operation, left UUO, or R-UUO procedu res at six rats per group. The sham, UUO, and R-UUO animals were studied 10 days after UUO or 7 days after R-UUO. A clear increase in the left (obstru cted) kidney's malondialdehyde (MDA), a marker of lipid peroxidation, was o bserved: a significant 2.6-fold of sham during UUO and a 1.7-fold of sham i n R-UUO. The contralateral (unobstructed) right kidney showed a significant rise in MDA during UUO, but during R-UUO the MDA had fallen back to sham v alues. It is possibly the result of a systemic effect from the free radical s produced by the oxidative stress of the UUO. The antioxidant enzyme, mang anese superoxide dismutase (MnSOD) of the left, obstructed kidney showed a significant reduction in UUO compared to that of the sham. Upon reversal of UUO (R-UUO), MnSOD was lower than that of the sham. The left kidney's HSP- 70 increased during UUO and was 3.7-fold that of sham (P < 0.05) but, durin g R-UUO, was not different from sham (P, ns). The contralateral (intact) ri ght kidneys' HSP-70 showed no change between sham, UUO, and R-UUO states. W e conclude that UUO gives rise to oxidative stress which is generalized in both the obstructed and the contralateral unobstructed kidney, as indicated by the elevation in kidney MDA content in both kidneys. The intrinsic cell ular antioxidant enzyme, manganese superoxide dismutase, showed a significa nt and generalized reduction in both UUO and R-UUO. In contrast, the HSP-70 was markedly elevated only in the obstructed kidney and not in the R-UUO o r in the contralateral kidney, suggesting that the elevation of HSP-70 is a specific and localized response to oxidative injury of UUO. (C) 1998 Acade mic Press.