Figure 2.
Schematic illustration of the induction and the multiple roles of NQO1. Chemoprotectants and xenobiotics may lead to expression of the NQO1 gene via the activation of AhR, Nrf2, or both. NQO1 catalyzes the two-electron reduction of quinones; it escapes the one-electron reduction and avoids subsequent redox cycling of the quinone derivatives and the formation of reactive oxygen species. Both gene therapy and novel pharmacological compounds may be applied to elevate the expression of NQO1 in cardiac and vascular systems. Upregulation of NQO1 may be a potential therapeutic strategy for cardiovascular protection from oxidative stress and inflammation. Oxidation of NADH/NADPH through the activation of NQO1 has been found to protect against dyslipidemia, glucose intolerance, hypertension, obesity, and metabolic syndrome. Other signaling pathways may also be associated with the effects of NQO1 on cardiovascular diseases. Abbreviations—ROS: reactive oxygen species; PI3K: phosphoinositide 3-kinase; AKT: serine/threonine-specific protein kinase; Nrf2: nuclear factor erythroid 2-related factor 2; AhR: aromatic hydrocarbon receptor; HTN: hypertension; MS: metabolic syndrome; PARP: poly (ADP-ribose) polymerase; NQO1: NAD(P)H:quinone oxidoreductase 1; Q: quinone; SQ: semiquinone; HO: hydroquinone; UQ: ubiquinone; TQ: α-tocopherol quinone; UQH2: hydroubiquinone; TQH2: α-tocopherol hydroquinone.