The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
trans-Activation of PPARα and PPARγ by Structurally Diverse Environmental Chemicals
Open accessAbstract
A large number of industrial chemicals and environmental pollutants, including trichloroethylene (TCE), di(2-ethylhexyl)phthalate (DEHP), perfluorooctanoic acid (PFOA), and various phenoxyacetic acid herbicides, are nongenotoxic rodent hepatocarcinogens whose human health risk is uncertain. Rodent model studies have identified the receptor involved in the hepatotoxic and hepatocarcinogenic actions of these chemicals as peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear receptor that is highly expressed in liver. Humans exhibit a weak response to these peroxisome proliferator chemicals, which in part results from the relatively low level of PPARalpha expression in human liver. Cell transfection studies were carried out to investigate the interactions of peroxisome proliferator chemicals with PPARalpha, cloned from human and mouse, and with PPARgamma, a PPAR isoform that is highly expressed in multiple human tissues and is an important regulator of physiological processes such as adipogenesis and hematopoiesis. With three environmental chemicals, TCE, perchloroethylene, and DEHP, PPARalpha was found to be activated by metabolites, but not by the parent chemical. A decreased sensitivity of human PPARalpha compared to mouse PPARalpha to trans-activation was observed with some (Wy-14, 643, PFOA), but not other, peroxisome proliferators (TCE metabolites, trichloroacetate and dichloroacetate; and DEHP metabolites, mono[2-ethylhexyl]phthalate and 2-ethylhexanoic acid). Investigation of human and mouse PPARgamma revealed the transcriptional activity of this receptor to be stimulated by mono(2-ethylhexyl)phthalate, a DEHP metabolite that induces developmental and reproductive organ toxicities in rodents. This finding suggests that PPARgamma, which is highly expressed in human adipose tissue, where many lipophilic foreign chemicals tend to accumulate, as well as in colon, heart, liver, testis, spleen, and hematopoietic cells, may be a heretofore unrecognized target in human cells for a subset of industrial and environmental chemicals of the peroxisome proliferator class.
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Cites
Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators
Issemann, I., & Green, S. (1990) · Nature · doi:10.1038/347645a0 · Cited by 3,519
Kliewer, S. A., Sundseth, S. S., Jones, S. A., Brown, P. J., Wisely, G. B., Koble, C. S., Devchand, P., Wahli, W., Willson, T. M., Lenhard, J. M., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4318 · Cited by 2,164
Cited by
Perfluoroalkyl Acids: A Review of Monitoring and Toxicological Findings
Lau, C., Anitole, K., Hodes, C., Lai, D., Pfahles-Hutchens, A., & Seed, J. (2007) · Toxicological Sciences · doi:10.1093/toxsci/kfm128 · Cited by 2,620
EDC-2: the endocrine society's second scientific statement on endocrine-disrupting chemicals
Gore, A. C., Chappell, V. A., Fenton, S. E., Flaws, J. A., Nadal, A., Prins, G. S., Toppari, J., & Zoeller, R. T. (2015) · Endocrine Reviews · doi:10.1210/er.2015-1010 · Cited by 2,407
The toxicology of perfluorooctanoate
Kennedy, G. L., Butenhoff, J. L., Olsen, G. W., O'Connor, J. C., Seacat, A. M., Perkins, R. G., Biegel, L. B., Murphy, S. R., & Farrar, D. G. (2004) · Critical Reviews in Toxicology · doi:10.1080/10408440490464705 · Cited by 742
Reproductive and Developmental Toxicity of Phthalates
Lyche, J. L., Gutleb, A. C., Bergman, Å., Eriksen, G. S., Murk, A. J., Ropstad, E., Saunders, M., & Skaare, J. U. (2009) · Journal of Toxicology and Environmental Health, Part B · doi:10.1080/10937400903094091 · Cited by 607
Hatch, E. E., Nelson, J. W., Qureshi, M. M., Weinberg, J., Moore, L. L., Singer, M., & Webster, T. F. (2008) · Environmental Health · doi:10.1186/1476-069x-7-27 · Cited by 436
Metadata
- Authors
- Maloney, E. K., & Waxman, D. J.
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 161
- Issue
- 2
- Pages
- 209-218
- ISSN
- 0041-008X (ISSN-L)
- OpenAlex
- W2097049516
- Cited by
- 374
- References
- 2
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
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