Inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on cAMP-induced differentiation of rat C6 glial cell line.
Dioxin is suspected to cause adverse effects on the development of the central nervous system (CNS). To investigate the neurotoxic effects of dioxin on the differentiation of astrocytes, rat C6 glial cell line was used as a model, because these cells are induced to express astrocyte markers and to change the cell morphology toward an astrocytic phenotype by increasing intracellular cAMP levels. When C6 cells were simultaneously exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and N(6),O(2')-dibutylyl cAMP (dbcAMP), the expression of cytochrome P-450 1A1 (CYP1A1) was dramatically increased, and the expression of aryl hydrocarbon receptor (AhR) was moderately decreased in a dose-dependent manner. In addition, extension of astrocytic processes was inhibited by 1 nM TCDD that did not reduce cell viability. TCDD also inhibited the induction of glial fibrillary acidic protein (GFAP) expression in a dose-dependent manner, until the end of a 72-hr exposure period. This inhibition was restored by the addition of an antagonist of AhR, alpha-naphthoflavone. These results indicate that TCDD inhibits astrocytic differentiation of C6 cells, which may be mediated by an AhR-dependent pathway.
Takanaga
H
H
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. takanagah@pharm.kitasato-u.ac.jp
Kunimoto
M
M
Adachi
T
T
Tohyama
C
C
Aoki
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000187:drug effects* / Q000378:metabolism; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects* / Q000378:metabolism; D008969:Molecular Sequence Data; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000378:metabolism; D013723:Teratogens / Q000494:pharmacology*
D005904:Glial Fibrillary Acidic Protein; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; D000242:Cyclic AMP; D019363:Cytochrome P-450 CYP1A1