Metabolic Basis for Thyroid Hormone Liver Preconditioning: Upregulation of AMP-Activated Protein Kinase Signaling

Figure 3

Genomic signaling mechanisms in T₃ calorigenesis and liver reactive oxygen species (ROS) production leading to (A) upregulation of cytokine expression in Kupffer cells and hepatocyte activation of genes conferring cytoprotection, (B) Nrf2 activation controling expression of antioxidant and detoxication proteins, and (C) activation of the AMPK cascade regulating metabolic functions. Abbreviations: AP-1, activating protein 1; ARE, antioxidant responsive element; CaMKKβ, Ca²⁺-calmodulin-dependent kinase kinase-β; CBP, CREB binding protein; CRC, chromatin remodelling complex; EH, epoxide hydrolase; HO-1, hemoxygenase-1; GC-Ligase, glutamate cysteine ligase; GPx, glutathione peroxidase; G-S-T, glutathione-S-transferase; HAT, histone acetyltransferase; HMT, histone arginine methyltransferase; IL-1 (6), interleukin 1 (6); iNOS, inducible nitric oxide synthase; LKB1, tumor suppressor LKB1 kinase; MnSOD, manganese superoxide dismutase; MRPs, multidrug resistance proteins; NF-κB, nuclear factor-κB; NQO1, NADPH-quinone oxidoreductase-1; NRF-1 (2), nuclear respiratory factor-1 (2); Nrf2, nuclear receptor-E2-related factor 2; PCAF, p300/CBP-associated factor; RXR, retinoic acid receptor; PGC-1, peroxisome proliferator-activated receptor-γ coactivator-1; QO₂, rate of O₂ consumption; STAT3, signal transducer and activator of transcription 3; TAK1, transforming-growth-factor-β-activated kinase-1; TNF-α, tumor necrosis factor-α; TR, T₃ receptor; TRAP, T₃-receptor-associated protein; TRE, T₃ responsive element; UCP, uncoupling proteins; (—), reported mechanisms; (- - - -), proposed mechanisms.