Fig. 5: Doxorubicin-induced apoptosis.
From: Regulated cell death pathways in doxorubicin-induced cardiotoxicity
Schematic representation of doxorubicin-induced apoptosis in the heart. Doxorubicin-induced upregulation of p53, Bax/Bak, and downregulation of GATA4 and Bcl-XL activating caspases 9, 3, and 7 resulting in apoptotic death. Mitochondrial calcium overload and activation of mitochondrial permeability transition pore (mPTP) lead to mitochondrial membrane potential loss, mitochondrial swelling, and outer membrane rupture allowing the release of endonuclease G (EndoG), cytochrome c and activation of caspase 9. Doxorubicin induces the extrinsic apoptotic pathway via the upregulation of death receptors and the activation of NFAT and NF-κΒ. DR: death receptor, TNFR1 tumor necrosis factor receptor 1, FADD Fas-associated protein with death domain, DR death receptor, lipid-OO lipid peroxides, EndoG endonuclease G, Ca2+ calcium, ROS reactive oxygen species, mPTP mitochondrial permeability transition pore, MOMP mitochondria outer membrane permeability, DOX doxorubicin, Bax Bcl-2-associated X protein, Apf-1 apoptosis protease factor-1, BID BH3 interacting-domain death, NF-κΒ nuclear factor-κB, NFAT4 nuclear factor of activated T-cells, GATA4 GATA-binding protein 4.
