Summary of liver GAPDH changes in response to combined ethanol and APAP exposure and the effects of TCH346 treatment.
Combined ethanol and APAP mediated mouse liver injury is associated with a significant increase in GAPDH nuclear translocation and cytoplasmic aggregation. The drug TCH346, which was previously shown to target GAPDH in the brain, attenuates liver injury in association with EtOH+APAP treatment. The mechanism by which TCH346 exerts its effect in this liver injury model are independent of GAPDH nuclear levels and aggregation, but involve mitochondrial events. TCH346 treatment is associated with increased mitochondrial Complex I activity and cytochrome c levels, and decreased CPS-1, which may be nitrated and/or non-functional .