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Event: 17
Key Event Title
Altered gene expression, AHR nuclear translocator (ARNT)-dependent pathway
Short name
Biological Context
Level of Biological Organization |
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Molecular |
Cell term
Organ term
Key Event Components
Key Event Overview
AOPs Including This Key Event
AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
---|---|---|---|---|
AHR activation leading to lung cancer via AHR-ARNT tox path | KeyEvent | Dianke Yu (send email) | Under development: Not open for comment. Do not cite | |
AHR activation decreasing lung function via AHR-ARNT tox path | KeyEvent | Dianke Yu (send email) | Under development: Not open for comment. Do not cite |
Stressors
Taxonomic Applicability
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Sex Applicability
Key Event Description
Sustained AHR/ARNT dimerization induced by DLCs may sequester ARNT from its other dimerization partners at inappropriate times during embryonic cardiomorphogenesis, disrupting ARNT-dependent cellular functions[1][2]. ARNT serves as a dimerization partner for hypoxia inducible factor 1&alph; (HIF-1α), and this complex is involved in mediating physiological responses to hypoxia. Dimerization between ARNT and HIF-1α forms a transcription factor complex (HIF-1) that binds to hypoxia response enhancer sequences on DNA to activate the expression of genes such as vascular endothelial growth factor (VEGF), which is involved in angiogenesis[3][4][5][6][7].
How It Is Measured or Detected
Domain of Applicability
References
- ↑ Heid, S. E., Walker, M. K., and Swanson, H. I. (2001). Correlation of cardiotoxicity mediated by halogenated aromatic hydrocarbons to aryl hydrocarbon receptor activation. Toxicol.Sci 61, 187-196.
- ↑ Walker, M. K., Pollenz, R. S., and Smith, S. M. (1997). Expression of the aryl hydrocarbon receptor (AhR) and AhR nuclear translocator during chick cardiogenesis is consistent with 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced heart defects. Toxicol.Appl.Pharmacol. 143, 407-419.
- ↑ Forsythe, J. A., Jiang, B. H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., and Semenza, G. L. (1996). Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol.Cell Biol. 16, 4604-4613.
- ↑ Goldberg, M. A., and Schneider, T. J. (1994). Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin. J.Biol.Chem. 269, 4355-4359.
- ↑ Jiang, B. H., Rue, E., Wang, G. L., Roe, R., and Semenza, G. L. (1996). Dimerization, DNA binding, and transactivation properties of hypoxia-inducible factor 1. J.Biol.Chem. 271, 17771-17778.
- ↑ Maxwell, P. H., Dachs, G. U., Gleadle, J. M., Nicholls, L. G., Harris, A. L., Stratford, I. J., Hankinson, O., Pugh, C. W., and Ratcliffe, P. J. (1997). Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc.Natl.Acad.Sci U.S.A 94, 8104-8109.
- ↑ Shweiki, D., Itin, A., Soffer, D., and Keshet, E. (1992). Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359, 843-845.