FIG. 8.

Hypothetical oxidative stress and antioxidant responses in ts1-infected astrocytes. In this schematic diagram, gPr80^env retention in the ER initiates ER stress with Ca²⁺ release and subsequent Ca²⁺ overload-induced mitochondrial stress. This is followed by overproduction of ROS (H₂O₂) and decreased GSH content in the cells. ROS accumulation and GSH depletion then trigger the activation and nuclear translocation of Nrf-2, which activates transcription of genes having Nrf-2-binding ARE elements in their promoters. The upregulated products of these genes (xCT, γ-GCL, and GPx, here highlighted in gold) function to upregulate cystine uptake and GSH biosynthesis and activity. Antioxidant enzymes catalase, Cu/Zn SOD, and Mn SOD are not upregulated. CSSC, cystine; Glu, glutamate; γGluCys, γ-glutamylcysteine; Gly, glycine; GS, GSH synthetase; GSSG, oxidized form of GSH.