The protective effect of peroxiredoxin II on oxidative stress induced apoptosis in pancreatic β-cells

Excessive loss of pancreatic β-cell mass, mainly due to apoptosis, is a major cause in the development of diabetic hyperglycemia in both type 1 and type 2 diabetes mellitus [1]. β-cell apoptosis is initiated by a variety of stimuli such as inflammatory cytokines, chronic hyperglycemia and hyperlipidemia [2,3] and downstream effects such as endoplasmic reticulum stress [4] and mitochondrial dysfunction [5]. Oxidative stress plays a permissive role in the process of apoptosis leading to cell destruction in many types of cell lineages [6,7]. Particularly the β-cells are more susceptible to oxidative stress due to the fact that they express major antioxidants such as superoxide dismutase, catalase and glutathione peroxidase at low levels [1,8,9]. In the pancreatic islets, superoxide dismutase expression is 30-40% compared with that of the liver, glutathione peroxidase expression is 15%, and catalase expression cannot be detected [10].At the cellular level, oxidative stress-mediated β-cell apoptosis can result from an imbalance between reactive oxygen species (ROS) generation and its clearance by antioxidants [9]. It has been demonstrated that proinflammatory cytokines induced β-cell apoptosis is mediated through elevation of ROS in the mitochondria via altered electron transport chain action [11], and increased nitric oxide (NO) production via activation of inducible nitric oxide synthase (iNOS) [12]. The process is known to be involved with activation of the nuclear factor-κB (NF-κB) and the c-Jun N-terminal kinase (JNK/SAPK) or the FAS-FAS ligand pathways [13]. Induction of ROS is found to be multilateral. Long chain saturated non-esterized fatty acids (NEFA) such as palmitic acid (PA) induces ROS production in the mitochondria through the electron transport chain [11,14]. The long chain saturated NEFAs could also directly interact with respiratory chain proteins and increase the oxygen radicals [15]. Streptozotocin (STZ) is a toxic agent that causes β-cell death via