Exercise preconditioning reduces acute ischemic renal injury in Hsp70.1 knockout mouse

Abstract

Backgroun/aims: Heat shock protein 70 (Hsp70) is an anti-apoptotic protein that has a protective effect in renal ischemic injury. Exercise up-regulates Hsp family proteins (Hsps), antioxidants and antiapoptotic proteins. We hypothesized that exercise as preconditioning could attenuate acute renal dysfunction and apoptosis resulting from renal ischemic injury under the Hsp70 deficient circumstance and could contribute to the prevention of renal injury induced by ischemia. Method: To investigate the effect of exercise preconditioning on protecting the kidney from ischemia in Hsp70 deficiency, we measured apoptosis-related factors and Hsps. Hsp70.1 KO and wild-type mice were divided into sham control (Sham), exercise preconditioning (Ex), renal ischemia-after-exercise (Ex+IR), and ischemia (IR) groups. Where appropriate a treadmill exercise was performed at 20 m/min, 60 min per day on a 0% gradient for 7 days, and renal ischemia was induced by clamping the renal pedicle for 25 min. To characterize the effects of exercise on oxidative stress- and apoptosis-related factors, and Hsp27 and 70 expressions, we performed immunohistochemistry, western blotting and TUNEL assay, and also measured level of serum creatinine. Results: Serum creatinine concentration and 4-HNE expression were raised in the IR group, as were caspases 3, 7 and 9, while Cu- and Mn-SOD levels were reduced, as were those of anti-apoptotic proteins Bcl-XL, Bcl-2 and Hsp27. All these effects were largely reversed by the exercise preconditioning, as was the decrease in apoptotic cells observed after exercise preconditioning. Conclusion: Exercise preconditioning has a beneficial effect in inhibiting oxidative stress and apoptotic cell death in the kidney resulting from ischemic injury even under Hsp70 deficiency.