Banerjee Sumita, Mukherjee Saikat, Mitra Sanjib, Singhal Pallav
Department of Oral Pathology, Dental College, Regional Institute of Medical Sciences.
Department of Biochemistry, Manipur University.
J Oral Sci. 2017;59(3):439-446. doi: 10.2334/josnusd.16-0655.
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.
活性氧物种如果因氧化磷酸化产生过量，会导致线粒体DNA损伤和进行性呼吸链功能障碍，进而引发包括致癌作用在内的各种疾病。由于缺乏内含子、保护性组蛋白和DNA修复酶，线粒体易受氧化应激（OS）影响。然而，线粒体受到多种抗氧化剂的保护，如超氧化物歧化酶2（SOD2）、过氧化氢酶、谷氧还蛋白2（GLRX2）、还原型谷胱甘肽（GSH）、谷胱甘肽过氧化物酶（GPX）和硫氧还蛋白2（TXN2）。为了深入了解这些线粒体抗氧化剂在口腔鳞状细胞癌（OSCC）中的表达情况，我们通过用针对抗氧化酶的特异性抗体进行免疫印迹和/或生化分析，对OSCC不同阶段线粒体抗氧化剂的关键分子成分进行了定性和定量评估。随着OSCC的进展，不同的线粒体抗氧化剂表达水平有所不同。随着OSCC的进展，GPX1、GPX4和过氧化氢酶的水平降低。然而，GLRX2、PXR3、TXN2和还原型GSH逐渐增加。SOD2的表达在OSCC的II期和III期最初下降，但在IV期增加。总之，我们的研究结果表明，在OSCC的不同阶段，各种线粒体抗氧化剂之间存在复杂的相互作用，对这些分子成分的进一步深入了解有助于我们在线粒体氧化还原状态的背景下更好地理解OSCC的发病机制。
