The mechanism and therapeutic strategies in doxorubicin-induced cardiotoxicity: Role of programmed cell death

Figures

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  Fig. 1. Schematic diagram of the mechanism of apoptosis, pyroptosis, and necroptosis. Abbreviations used: DOX, doxorubicin; METRNL, Meteorin-like; SIRT1, sirtuin deacetylase (silent information regulator 2 [Sir2]) 1; DAXX, death domain-associated protein; IL, interleukin; TOP-2β, topoisomerase 2β; PDE10A, phosphodiesterase 10A; PARP, nuclear enzyme poly (ADP-ribose) polymerase; ROS, reactive oxygen species; MMP, mitochondrial membrane potential; TLR4, toll-like receptor 4; GSDMD, gasdermin D; Bnip3, BH3-only protein Bcl-2/adenovirus E1B 19-kDa-interacting protein 3; NLRP3, nucleotide-binding domain-like receptor protein 3; GSK-3β, glycogen synthase kinase 3β; TNF-α, tumor necrosis factor-alpha; CAMKII, calcium/calmodulin-dependent protein kinase II association domain; RIPK, receptor-interacting serine/threonine-protein kinase; PGC-1α, peroxisome proliferator-activated receptor gamma co-activator 1-alpha; MLKL, mixed lineage kinase domain-like protein; TRADD, tumor necrosis factor receptor type 1 associated death domain protein; FADD, Fas-associated protein with death domain; Bcl-2, B-cell lymphoma 2.

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  Fig. 2. Schematic diagram of the mechanism of autophagy and ferroptosis. Abbreviations used: DOX, doxorubicin; Bnip3, BH3-only protein Bcl-2/adenovirus E1B 19-kDa-interacting protein 3; ROS, reactive oxygen species; TFEB, transcription factor EB; LCN2, lipocalin-2; GSDMD, gasdermin D; FAM134B, an endoplasmic reticulum autophagy receptor; LC3, autophagic protein; SIRT, sirtuin deacetylase (silent information regulator 2 [Sir2]); RRM2, ribonucleotide reductase M2 subunit; Lamp2A, lysosomal-associated protein 2a; Alas1, aminolevulinate synthase 1; 5-ALA, 5-aminolevulinic acid; GPX4, glutathione peroxidase 4; SLC7A11, solute carrier family 7 member 11; EP1, E-prostanoid 1 receptor; PRMT4, protein arginine methyltransferase 4; Nrf2, nuclear factor erythroid 2-related factor 2; CYLD, cylindromatosis; SPATA2, spermatogenesis-associated protein 2; Bcl-2, B-cell lymphoma 2.

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  Fig. 3. Schematic representation of the role of oxidative stress, inflammation, and mitochondrial dysfunction in DOX-induced cardiotoxicity. Abbreviations used: DOX, doxorubicin; Nrf2, nuclear factor erythroid 2-related factor 2; RIPK1, receptor-interacting serine/threonine-protein kinase 1; KNG1, kininogen-1; FNDC5, fibronectin type III domain-containing 5; MON, monotropein; ROS, reactive oxygen species; NLRP3, nucleotide-binding domain-like receptor protein 3; ASC, apoptosis-associated speck-like protein containing a CARD; NF-κB, nuclear factor-κB; GSDMD, gasdermin D; AMPK, adenosine monophosphate-activated protein kinase; NOX, nicotinamide adenine dinucleotide phosphate oxidase; DRP1, dynamin-related protein 1; PGC-1α, peroxisome proliferator-activated receptor gamma co-activator 1-alpha; Bnip3, Bcl2/adenovirus E1B 19 kDa protein-interacting protein 3; mPTP, mitochondrial permeability transition pore; cypD, cyclophilin D; FIS1, mitochondrial fission 1 protein.