Hyperglycemia induces apoptosis and p53 mobilization to mitochondria in RINm5F cells

The mechanisms related to hyperglycemia-induced pancreatic β-cell apoptosis are poorly defined. Rat insulin-producing cells (RINm5F) cultured in high glucose concentrations (30 mM) showed increased apoptosis and protein p53 translocation to mitochondria. In addition, hyperglycemia induced both the disruption of mitochondrial membrane potential (Δ < eqid1 > _m), and an increase in reactive oxygen species (ROS), as shown by fluorescence changes of JC-1 and dichlorodihydrofluorescein-diacetate (DCDHF-DA), respectively. The increased intracellular ROS by high glucose exposure was blunted by mitochondrial-function and NADPH-oxidase inhibitors. We postulate that the concomitant mobilization of p53 protein to the mitochondria and the subsequent changes on the Δ < eqid2 > _m, lead to an important pancreatic β-cell apoptosis mechanism induced by oxidative stress caused by hyperglycemia. This work is part of the thesis required for the doctorate degree in Biological Sciences at the Universidad Autónoma Metropolitana, Mexico City, Mexico.