G6PD off-target effect significantly alters intracellular redox capacity in knockdown cell lines. Model predicted dynamics of intracellular H2O2 accumulation (first column), glutathione redox potential (second column), thioredoxin redox potential (third column), and Pr-SSG accumulation (fourth column) in the Grx1 knockdown cell line after a 100 μM extracellular H2O2 treatment. Solid black lines represent the model-predicted behavior for the ideal knockdown cell lines with no off-target effects (Grx1), red dashed lines represent the model-predicted behavior for the experimentally characterized shRNA cell lines with all qRT PCR-determined off-target effects except those affecting the G6PD enzyme, and blue dotted lines represent the model-predicted behavior for Grx1 silencing only in the presence of G6PD off-target effects.
Kippner et al. BMC Systems Biology 2011 5:164 doi:10.1186/1752-0509-5-164