Caspase 3 in the pathogenesis of diabetic nephropathy: relationship with NF-κB gene expression and AOPP
Diabetic nephropathy (DN) is the most common and prevalent complication of diabetes mellitus (DM). Persistent hyperglycemia was induced oxidative stress,leading to cell damage and death by apoptosis,and enhanced the development of DN. However,the mechanism by which hyperglycemia induces apoptosis is not well understood. 60 patients (30 patients with Typ2 DM,30 patients with DN) and 30 healthy subjects as control group were enrolled in this study. Serum levels of advanced oxidation protein products (AOPPs) and CAT activity as indirect markers of oxidative stress were measured by the colorimetric method,level of serum caspase-3 as a proapoptotic biomarker was also measured by ELISA. Additionally,expression of the apoptotic genes,nuclear factor-B (NF-κB) in serum was investigated using qPCR. The level of AOPP was significantly increased in DN and DM group than control (P <0.05),while CAT activity in DN significantly decrease (P< 0.05) as compared with DM and control groups. Levels of caspase-3 in DN patients were significantly higher than DM and control groups (𝑃< 0.05),with upregulation of NF-κB mRNA gene expression.This study identified caspase-3 as a final common mediator of high glucose-induced apoptosis and have an important role in DN pathogenesis and progression. Apoptosis seems to be associated with an alteration in inflammatory mediators such as oxidative stress.