Cardiac PTN-SIRT1 axis alleviates oxidative stress and promotes mitochondrial energy reprogramming to mitigate doxorubicin-induced cardiotoxicity through AMPK/PGC1α signaling

• PTN is downregulated in doxorubicin-induced cardiotoxicity, and its overexpression alleviates cardiac injury in vitro and in vivo. • PTN directly binds SIRT1 and activates AMPK phosphorylation at Thr172, triggering the AMPK-PGC1α axis to reprogram mitochondrial energy metabolism. • The PTN-SIRT1 axis reduces mitochondrial oxidative stress and apoptosis, restoring energy production and cardiac function. • This study identifies the PTN-SIRT1 axis as a novel therapeutic target for preventing chemotherapy-related cardiac injury.