Figure 7.

Spermidine attenuates H₂O₂-induced cellular dysfunction via suppression of Ca²⁺ signaling pathways in ARPE-19 cells. Oxidative stress by H₂O₂ triggers apoptosis through the intrinsic and extrinsic pathways in ARPE-19 cells. Spermidine markedly attenuated mitochondrial and nuclear dysfunction upon oxidative stress, inhibiting apoptosis. Spermidine suppresses intracellular Ca²⁺ levels and repairs ER damage, creating the anti-apoptotic effects. Nevertheless, while spermidine has antioxidant capacity, it does not down-regulate intracellular ROS generation during oxidative stress. Taken together, spermidine suppresses oxidative stress-induced cellular dysfunction via suppression of Ca²⁺ signaling pathways in ARPE-19 cells independently of ROS generation.