Fig. 3.

Fragment 1–36 a.a. of the HCV core protein activates the Nrf2/ARE cascade by the ROS-independent mechanism involving casein kinase 2 and phosphoinositide 3-kinase; the 37–191 a.a. fragment – by the ROS-dependent mechanism involving protein kinase C. The role of protein kinases and reactive oxygen species was estimated by measuring luciferase expression in Huh7 cells co-transfected with the reporter pP-ARE plasmid with constructs encoding the full-length core protein (A) or its fragments 1–36 a.a. (B) and 37–191 a.a. (C) or by an analysis of the intracellular localization of Nrf2 (D). The latter was studied by separation of cytoplasmic (Cyt) and nuclear (Nu) protein fractions, with subsequent detection of Nrf2 by immunoblotting. Inhibitors of protein kinases Ro 31-8220 (Ro, protein kinase C inhibitor), DRB (casein kinase 2 inhibitor), or wortmannin (Wo, phosphoinositide 3-kinase inhibitor) in the absence or presence of an antioxidant pyrrolidine dithiocarbamate (PDTC) were added into the culture medium 18 h post-transfection. *p < 0.01.