Altered expression of mitochondrial antioxidants in oral squamous cell carcinoma.

Abstract

Reactive oxygen species, if produced in excess by oxidative phosphorylation, contributes to mitochondrial DNA damage and progressive respiratory chain dysfunction, leading to various diseases including carcinogenesis. Mitochondria are susceptible to oxidative stress (OS) owing to lack of introns, protective histones, and DNA repair enzymes. However, mitochondria are protected from OS by numerous antioxidants such as superoxide dismutase 2 (SOD2), catalase, glutaredoxin 2 (GLRX2), reduced glutathione (GSH), glutathione peroxidase (GPX), and thioredoxin 2 (TXN2). To obtain insights regarding expression of these mitochondrial antioxidants in oral squamous cell carcinoma (OSCC), we performed qualitative and quantitative estimations of key molecular players of mitochondrial antioxidants during various stages of OSCC by immunoblotting with specific antibodies against antioxidant enzymes and/or biochemical assays. Different mitochondrial antioxidants varied in their expression levels as OSCC progressed. The levels of GPX1, GPX4, and catalase reduced with progression of OSCC. However, GLRX2, PXR3, TXN2, and reduced GSH gradually increased. Expression of SOD2 decreased initially in Stages II and III of OSCC but increased in Stage IV. In conclusion, our findings indicate a complex interplay of various mitochondrial antioxidants in different stages of OSCC, and further insights regarding these molecular players can help us better understand the pathogenesis of OSCC in context of mitochondrial redox status.