NADPH Oxidase Activation Is Required in Reactive Oxygen Species Generation and Cell Transformation Induced by Hexavalent Chromium

• DOI: 10.1093/toxsci/kfr180
• Publication Date: 2011-07-09T02:28:57Z
• Authors: Xin Wang; Young-Ok Son; Qingshan Chang; Lijuan Sun; J.Andrew Hitron; Amit Budhraja; Zhuo Zhang; Zunji Ke; Fei Chen; Jia Luo; Xianglin Shi
• Keywords: NOX1; Hexavalent Chromium; SOD2; P22phox

Hexavalent chromium [Cr(VI)] is a well-known human carcinogen associated with the incidence of lung cancer. Although overproduction reactive oxygen species (ROS) has been suggested to play major role in its carcinogenicity, mechanisms Cr(VI)-induced ROS production remain unclear. In this study, we investigated NADPH oxidase (NOX), one sources cellular ROS, oxidative stress and carcinogenesis. We found that short-term exposure Cr(VI) (2μM) resulted rapid increase generation Beas-2B cells, concomitantly increased NOX activity expression members (NOX1-3 NOX5) subunits (p22(phox), p47(phox), p40(phox), p67(phox)). also induced phosphorylation p47(phox) membrane translocation p67(phox), further confirming activation. Knockdown short hairpin RNA attenuated by Cr(VI). Chronic (up 3 months) low doses (0.125, 0.25, 0.5μM) promoted subunits, such as but inhibited main antioxidant enzymes, superoxidase dismutase (SOD) glutathione peroxidase (GPx). transformation increasing cell proliferation, anchorage independent growth soft agar, forming aggressive tumors nude mice. Stable knockdown or overexpression SOD1, SOD2, catalase (CAT) eliminated malignant transformation. Our results suggest plays an important