Sirtuin 1 enzyme activity and autophagy proteins are increased in the kidney during murine sepsis

Abstract

Sepsis affects over 750,000 patients annually and the development of acute kidney injury (AKI) during sepsis nearly doubles the mortality rate to 75%. We have recently published that the dietary antioxidant, resveratrol (RSV), can improve kidney function and survival in the cecal ligation and puncture (CLP) model of sepsis in the mouse. Since RSV has been reported to lead to the activation of sirtuin1 (SIRT1), which may be protective, we investigated the relationship between SIRT1 and acetylation of p53. SIRT1 enzyme activity was increased at 10 and 18h post CLP as were the autophagy‐related proteins Atg5 and LC3. Moreover, acetylated p53 levels were significantly increased at 6h and 10h, but not 18h. By immunostaining, the number of TUNEL‐positive cells was increased by sepsis and acetylated p53 was localized mainly to the cytoplasm of proximal tubular epithelial cells in the cortex and cortico‐medullary junction. While RSV (10 mg/kg, ip) did not increase SIRT1 activity, RSV did block the increase in acetylated p53. These data suggest that CLP causes both autophagy and apoptosis in the kidney and that RSV may dampen the apoptotic response. Supported by F30 DK085705 (JHH) and R01 DK075991 (PRM).