Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Abstract

Reports about the peroxisomes of rat liver are abundant, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] but much less is known about those of other rat organs. 17,18) Furthermore, there are few reports about peroxisomes of human liver, 2,3,5,6,[8][9][10]14,19) and very few about those of other human organs. [20][21][22] There are three kinds of trophoblasts in the placenta: cytotrophoblasts, syncytiotrophoblasts and extravillous trophoblasts. Each of the three plays important roles in the development and maintenance of gestation. In human trophoblasts, peroxisomes are known to be present in cytotrophoblast cells, 20,22) and are detected later during gestation in syncytiotrophoblast cells. 22)However, extravillous trophoblast cells are difficult to obtain; therefore peroxisomes in these cells have not yet been elucidated.Clofibric acid (a fibric acid derivative) is a hypolipidemic agent. This agent, at least, is thought to suppress the synthesis of cholesterol by inhibiting 3-hydroxy-3-methylglutarylCoA reductase (HMG-CoA reductase), the rate-limiting enzyme of cholesterol synthesis in the whole body 23,24) and cell cultures.13) We previously reported the effects of clofibrate and gemfibrozil (one of the fibric acid derivatives) on the synthesis of isoprenoid lipids such as ubiquinone, dolichol and cholesterol in the whole body and cultured cells of rats. 13,15,25) Almost all of the hormone-producing cells secrete either steroid hormone or protein hormone, but trophoblast cells secrete both. We previously reported that clofibric acid and gemfibrozil up-regulate progesterone (steroid hormone) secretions in human extravillous trophoblast cells using an immortalized trophoblast cell-line (TCL-1). 26,27) That is, clofibric acid and gemfibrozil activated steroid hormone synthesis although these substances are inhibitors of HMG-CoA reductase. Steroid hormone is synthesized from cholesterol. Peroxisomes take part in cholesterol synthesis.28) Sterol carrier protein 2 may participate in steroid hormone synthesis, [29][30][31] and is reported to be primarily localized in peroxisomes. [32][33][34] We detected catalase and fatty acyl-CoA oxidase activity in the homogenate of TCL-1 cells, 27) but whether peroxisomes are present in the cells has not been clarified. Therefore, using morphological and biochemical (cell fractionation) techniques, we studied the presence of peroxisomes in these extravillous trophoblast cells.Clofibrate is not only a hypolipidemic agent, but also a peroxisome proliferator-activated receptor a (PPARa) agonist in rodents. With respect to the effect of PPARa agonist on peroxisomal enzymes and proliferation, there are many reports about rat liver. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] In human liver cells, some reports demonstrated an increase in peroxisomal enzyme activity caused by PPARa agonist, 5,6,10,12,19) while others reported that there was no effect. 2,3,8,9,14) In all organs except the liver, the effects of PPAR agonist on peroxisomes are little reported in rats, 17...

Effects of WY-14643 on Peroxisomal Enzyme Activity and Hormone Secretion in Immortalized Human Trophoblast Cells

“…33,34) In the preceding paper, using morphological and biochemical methods, we clarified that clofibric acid induces the proliferation of microperoxisomes in human trophoblast cells. 4) We tried to purify the TCL-1 peroxisomes by a discontinuous Nycodenz density gradient centrifugation, but a small number of mitochondria contaminated the peroxisomal fractions (Fig. 2).…”

“…3) In the preceding paper, we clarified that clofibric acid induces the proliferation of trophoblast cell microperoxisomes. 4) Rat liver cells are useful for experiment of peroxisomes, but they do not secrete hormone. However, trophoblast cells secrete both steroid hormone and protein hormone.…”

“…4) In the present experiment, for good separation of the peroxisomes from other organella we performed a discontinuous Nycodenz density gradient centrifugation (1.12-1.16 g/ml) of the light mitochondrial fraction of the cells treated with WY-14643. We compared the result of WY-14643 with that of gemfibrozil and clofibric acid.…”

“…Namely, microperoxisomes, which have a density smaller than those of rat hepatic peroxisomes, exist in human extravillous trophoblast cells. 4) Clofibric acid and gemfibrozil (fibric acid derivative) are not only a hypolipidemic drug, but also a peroxisome proliferator-activated receptor (PPAR)a agonist in rodents. [5][6][7] However, it is unclear whether PPARa agonists affect peroxisomal enzyme activity in human liver cells.…”

Carbaprostacyclin, a PPARδ agonist, ameliorates excess lipid accumulation in diabetic rat placentas

“…Both PPARα and PPARδ agonists are able to induce the expression of ACO, the rate-limiting enzyme in peroxisomal β-oxidation, in different cell types (Mochizuki et al 2008;Nagasawa et al 2006). ACO is expressed in the human placenta (Hashimoto et al 2008). We here found that ACO is expressed in the rat placenta at midgestation, and that ACO expression is enhanced in the diabetic placenta when compared to controls.…”