Functional activation of peroxisome proliferator-activated receptor alpha (PPARalpha) by environmental chemicals in relation to their toxicities.
Peroxisome proliferator-activated receptor alpha (PPARalpha) may work in the processes of both physiological and toxicological response to various endogenous or exogenous substances. The literature on the study of functional activation of PPARalpha by environmental chemicals in relation to their toxicities were reviewed. Environmental chemicals that were found to induce peroxisomes (peroxisome proliferators) and to activate the function of PPARalpha included plasticizers, herbicides, and organic solvents that have carboxyl groups in their parent substances or their metabolites. Several studies have showed species differences in the constitutive expression of PPARalpha and activation of PPARalpha, which may result in species differences in the induction of transcription of the genes encoding several peroxisomal enzymes. Although much information has supported the view that PPARalpha is primarily involved in the hepatic carcinogenicity of peroxisome proliferators, conflicting evidence exists. Most of the peroxisome proliferators have been shown to induce reproductive and developmental disorders, which might, in part. be associated with the functional activation of PPARalpha. Few epidemiological studies on the effect of peroxisome proliferators on humans have been conducted. The effect of perfluorooctanoic acid on humans was evaluated from the aspect of lipid metabolism in one study, which concluded that there was no effect.
Nakajima
Tamie
T
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ka, Nagoya 466-8550, Japan. tnasu23@med.nagoya-u.ac.jp
Ichihara
Gaku
G
Kamijima
Michihiro
M
Itohara
Seiichiro
S
Aoyama
Toshifumi
T
D000818:Animals; D002274:Carcinogens, Environmental / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006540:Herbicides / Q000633:toxicity; D006801:Humans; D008024:Ligands; D008297:Male; D051379:Mice; D010968:Plasticizers / Q000633:toxicity; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D012997:Solvents / Q000633:toxicity; D014157:Transcription Factors / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
D002274:Carcinogens, Environmental; D004785:Environmental Pollutants; D006540:Herbicides; D008024:Ligands; D010968:Plasticizers; D018160:Receptors, Cytoplasmic and Nuclear; D012997:Solvents; D014157:Transcription Factors