Figure 7
Schematic summary of molecular events underlying O2−-mediated induction of S70pBcl-2 upon the downregulation of SOD1 in tumor cells. Augmented level of intracellular O2− as a result of SOD1 inhibition/downregulation could lead to an increase in the formation of ONOO− and the eventual tyrosine nitration of B56δ. This in turn inhibits the recruitment of PP2A-AC core subunits to Bcl-2, resulting in the accumulation of S70-phosphorylated Bcl-2 and the further inhibition of apoptotic stimuli. Redox modulators such as DPI, tiron, and FeTPPS may harbor the potential as chemosensitization agents by suppressing the levels of O2− or ONOO− in tumor cells.
