Abstract
Peroxiredoxin 6 (PRDX6) is a member of the PRDX family of antioxidant enzymes and correlated with inflammatory response. Therefore, we investigated the role of PRDX6 during lipopolysaccharide (LPS)-induced acute kidney injury. Both 3 months aged PRDX6-overexpressing transgenic mice (PRDX6 mice) and wild type (WT) mice had acute renal injury induced by intraperitoneal injection of LPS (10 mg/kg)., PRDX6 mice showed decreased mortality and renal injury following LPS challenge compared to WT mice. Furthermore, infiltration of macrophages, T-cells and neutrophils, and the number of apoptotic cells were more decreased by LPS treatment in PRDX6 mice than in WT mice. Because LPS induces reactive oxygen species (ROS) production which induces inflammation through c-Jun N-terminal Kinase (JNK) and p38 MAPK activation, we investigated ROS concentration and MAPK signaling pathway in the kidney of PRDX6 mice. As expected, LPS-induced oxidative stress was attenuated, and p38 MAPK and JNK activation was decreased in the kidney of PRDX6 mice. Inhibitory effect of PRDX6 on LPS-induced apoptosis and MAPK activation in the primary renal proximal tubular cells were overcome by treatment with PRDX6 inhibitor or hydrogen peroxide. These results suggest that PRDX6 overexpression inactivates p38 MAPK and JNK pathway through decrease LPS-induced ROS concentration in the kidney, resulting in inhibition of renal apoptosis and leukocyte infiltration and led to attenuation of LPS-induced acute kidney injury.
Highlights
Acute kidney injury (AKI), so called acute renal failure (ARF) is a disease which resulting in rapid loss of function in kidney with severe tubular damage
Because reactive oxygen species (ROS) play an important role in sepsis-induced acute kidney injury through activates Jun N-terminal Kinase (JNK) and p38 mitogenactivated protein kinases (MAPKs) resulting in inflammation and apoptosis [8,9,10, 23], we investigated the effect of Peroxiredoxin 6 (PRDX6) on oxidative stress in LPS-induced kidney tissues of mice
Because we observed that PRDX6 mice showed decreases in renal injury and oxidative stress in the kidney tissues after LPS challenge compared to wild type (WT) mice, we investigated that the effect of PRDX6 overexpression on renal apoptosis and oxidative stress in the primary renal proximal tubular cells from WT mice or PRDX6 mice
Summary
Acute kidney injury (AKI), so called acute renal failure (ARF) is a disease which resulting in rapid loss of function in kidney with severe tubular damage. It is a frequent and serious complication of sepsis and occurs approximately 19 percent of patient with moderate sepsis and 23 percent of patient with severe sepsis [1]. Lipopolysaccharide (LPS) is a component of outer membrane in Gram-negative bacteria and is involved in pathogenesis of sepsis-induced acute kidney injury [3, 4]. Numerous reports demonstrated that ROS involved in sepsis-induced acute kidney injury [8,9,10]. ROS may play a critical role in sepsis-induced acute kidney injury
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