Effects of WY-14643 on peroxisomal enzyme activity and hormone secretion in immortalized human trophoblast cells.
In our previous report, clofibric acid increased both the enzyme activities of peroxisomes (catalase and fatty acyl-CoA oxidase) and the secretion of progesterone in immortalized human extravillous trophoblast cells (TCL-1) (F. Hashimoto et al., Biochem. Pharm., 68, 313 (2004)). WY-14643 is reported to be stronger inducer of peroxisomes in rodents than clofibric acid. Therefore, the effects of WY-14643 on the activities of peroxisomal enzymes and hormone secretion in TCL-1 were studied. After incubation for 3 d with WY-14643, WY-14643 (>/=0.15 mM) suppressed the rate of increase in DNA and protein. The specific activities of catalase were increased by 0.1 mM WY-14643. The specific activities of fatty acyl-CoA oxidase were hardly changed by WY-14643. The concentration of progesterone in the medium was increased by 0.1 mM WY-14643, but human chorionic gonadotropin was decreased by 0.2 mM WY-14643. After a discontinuous Nycodenz-density gradient centrifugation of the light mitochondrial fraction of the cells, catalase activity was distributed in lower density fractions than cytochrome-c oxidase (a mitochondria marker enzyme) activity, but the distribution was not changed by WY-14643. These results suggest that WY-14643 inhibits the proliferation of trophoblast cells. The density of peroxisomes in human trophoblast cells is lower than that of mitochondria, and it is not affected by WY-14643. WY-14643 may increase the progesterone secretion. Effects of WY-14643 on metabolism of human trophoblast cells are different from those of clofibric acid.
Hashimoto
Fumie
F
Faculty of Pharmaceutical Sciences, Josai University. hasimoto@josai.ac.jp
Morita
Mieko
M
Iwasaki
Kaori
K
Takeda
Satoru
S
Hayashi
Hidenori
H
D042962:Acyl-CoA Oxidase / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism*; D018929:Cell Culture Techniques; D002460:Cell Line; D002499:Centrifugation, Density Gradient; D006063:Chorionic Gonadotropin / Q000378:metabolism; D002995:Clofibric Acid / Q000494:pharmacology; D015248:Gemfibrozil / Q000494:pharmacology; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D020675:Peroxisomes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D014327:Trophoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D006063:Chorionic Gonadotropin; D006728:Hormones; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D011374:Progesterone; D002995:Clofibric Acid; C006253:pirinixic acid; D002374:Catalase; D042962:Acyl-CoA Oxidase; D015248:Gemfibrozil