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Upon ligand binding, the AHR translocates to the nucleus, where it complexes with the AHR nuclear translocator (ARNT).
Upon binding to aromatic ligands, toxins, drugs, phytochemicals, and sterols, the AhR-ligand complex shuttles from cytoplasm to the nucleus, where it heteromerises with the AhR nuclear translocator (Arnt) to form the transcription complex able to bind to xenobiotic responsive elements (XRE) DNA-binding motifs located in the promoter region of the target drug metabolising genes, such as phase I (mainly, Cyp1 subfamily) and II metabolising enzymes and Nrf2 [156-158].
The CGA approach may be limited because of probe selection in the Affymetrix Styl array.Among 498 SNPs associated with candidate genes, only 9 were located within exons {CYPJA2, ARNT2 (aryl-hydrocarbon receptor nuclear translocator 2), EPHX1 [epoxide hydrolase 1, microsomal (xenobiotic)], EPHX2, CYP26B1, GSTM3 (glutathione S-transferase mu 3 (brain)], and CYP4B11 and 87 were located within introns.
Hitherto, the putative components include the voltage-dependent anion channel (VDAC) or porin, localized in the OMM; the adenine nucleotide translocator (ANT) in the IMM; the peripheral benzodiazepine receptor and the Bcl-2 family proteins; the hexokinase boundtoporin; the cyclophilin-D(Cyp-D), a regulatory element in the matrix; glycogen synthase kinase-3b (GSK-3b); and cytochrome c [121-123].
Most TCDD effects are mediated by its binding to the awl hydrocarbon receptor (AhR), leading to AhR nuclear translocation, heterodimerization with aryl hydrocarbon receptor nuclear translocator (ARNT), and binding to xenobiotic responsive elements present in the promoters of target genes (Barouki et al.
As a member of the PER-ARNT-SIM (PAS) domain family of transcriptional regulators, ligand-activated AhR translocates to the nucleus and heterodimerizes with AhR nuclear translocator (ARNT), leading to toxic responses (Bock 1994).
Vpr protein interacts with adenine nucleotide translocator (ANT, a component of mitochondrial permeability transition pore (PTP)) that is implicated in [Ca.sup.2+] influx into mitochondria.
Because AHR associates with proteasomal complexes consisting of damaged-DNA-binding protein 1, aryl hydrocarbon receptor nuclear translocator, transducin-[beta]-like 3, and cullin 4B and itself possesses E3 ligase activity (Ohtake et al.
[38] proposed the participation of the Adenine Nucleotide Translocator (ANT) in the mitochondria as a new mechanism of protection against increased ROS production in aged skeletal muscle.
Binding of TCDD to AHR causes the dissociation of the receptor from the complex and its translocation into the nucleus, where it dimerizes with the AHR nuclear translocator (ARNT).
Dioxin and the structurally related PCDF chemicals mediate their toxic effect (but with different potencies) mainly as a ligand to the same aryl hydrocarbon receptor (AHR)/AHR nuclear translocator (ARNT) complex that binds to the xenobiotic responsive element (XRE; also called dioxin-responsive element, DRE) on target DNA.
It has been demonstrated in hAPP mice that protein expression of some components of the MPT, such as cyclophilin D (CypD), voltage-dependent anion channel (VDAC), and adenine nucleotide translocator (ANT), is elevated.
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