Stimulation of peroxisomal palmitoyl‐CoA oxidase activity by ciprofibrate in hepatic cell lines: Comparative studies in Fao, MH<sub>1</sub>C<sub>1</sub> and HepG2 cells

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...

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Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Hashimoto

Shimooka

Iwasaki

et al. 2008

Biological & Pharmaceutical Bulletin

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“…As a marker of peroxisome proliferation, the palmitoyl-CoA oxidase activity was measured in parallel incubations without 32P,. This activity was assayed by the fluorometric measurement of H,O, produced, adapted to cell line samples (Brocard et al, 1993) according to the method previously reported (Vamecq, 1990). The H,O, reacts with homovanillic acid in the presence of peroxidase to give a fluorescent dimer.…”

Section: Chemicalsmentioning

confidence: 99%

“…Peroxisomal palmitoyl-CoA oxidase activity is widely used as a marker of peroxisome proliferation. Brocard et al (1993) have previously shown that palmitoyl-CoA oxidase activity is strongly induced by ciprofibrate in the Fao cell line while it is only weakly stimulated in HepG2 cells. In our experiments, the peroxisomal palmitoyl-CoA oxidase activity was measured in Fao and HepG2 cell lines after a treatment with ciprofibrate at 500 pM for 2 h. After this incubation time, no significant increase of the activity was observed in the two cell lines, while after 48 h at the same concentration of ciprofibrate, the activity was significantly induced 14-fold in Fao cells and no statistically significant changes were observed in HepG2 cells (Table 1).…”

Section: Lack Of Stimulated Phosphorylation Of Proteins In Humanmentioning

confidence: 99%

“…It is already known that there is no, or weak, peroxisome proliferation in human hepatic-derived cells (Hertz et al, 1987;Brocard et al, 1993). The reason for the lack of peroxisome proliferator effect in human cells is still poorly understood.…”

mentioning

confidence: 95%

“…The objective of this work was to compare the effect of ciprofibrate on the overall in vivo phosphoprotein levels between rat and human cells. We chose two derived hepatic cell lines: a rat hepatoma cell line, Fao, known to respond to peroxisome proliferators (Bayly et al, 1993), and a human hepatoblastoma cell line, HepG2, which does not experience peroxisome proliferation (Brocard et al, 1993). These two cell lines are known to be well differentiated on the basis of the expression of many liver-specific functions (Deschatrette et al, 1980;Javitt, 1990).…”

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confidence: 99%

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Influence of Peroxisome Proliferators on Phosphoprotein Levels in Human and Rat Hepatic-Derived Cell Lines

Passilly¹,

Jannin²,

Latruffe³

1995

Eur J Biochem

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To elucidate the effect of peroxisome proliferators on the signal-transduction pathway, we have compared the effect of ciprofibrate, an hypolipaemic agent, on the overall phosphoprotein level between rat and human well differentiated hepatic derived cell lines. The phosphorylation status of several phosphoproteins in the rat Fao cell line was increased by the drug while no changes were observed in the human HepG2 cell line. In rat Fao cells, this increase, which is concentration and time dependent, can be as much as eightfold for 20-kDa and 22-kDa proteins. Wy-14,643, a non-fibrate molecule and a more potent peroxisome proliferator than ciprofibrate, increased the phosphorylation status of the same phosphoproteins. Peroxisome proliferators may act by activating kinases inactive in control cells, by amplifying kinases already active in control cells or by inactivating phosphatases. The phosphoamino acid residues affected are essentially serine and threonine. This modification of the signal-transduction pathway by the peroxisome proliferators in rodent cells appears to be an early event or an independent mechanism of the peroxisome proliferation. These results support the accumulating evidence that the perturbation of this pathway may be a major cause of the hepatomegaly and the hepatocarcinogenesis induced by peroxisome proliferators in rodent species. In contrast, the lack of phosphorylation changes in the human HepG2 cell line supports the non-toxic effect of peroxisome proliferators also used as hypolipaemic agents in humans.

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Pristanic acid is activator of peroxisome proliferator activated receptor alpha

Hanhoff

Wolfrum

Ellinghaus

et al. 2001

Eur. J. Lipid Sci. Technol.

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Pristanic acid is activator of peroxisome proliferator activated receptor alpha lsoprenoid phytanic acid (3,7,11,15-tetramethylhexadecanoic acid) is degraded in peroxisomes by α-oxidation to pristanic acid (2,6,10,14-tetramethylpentadecanoic acid) and then via β-oxidation. Branched-chain phytanic acid is an activator of the peroxisome proliferator activated receptor α (PPARα) which in liver cells regulates expression of genes encoding peroxisomal and mitochondrial β-oxidative enzymes as well as cytosolic/nuclear liver-type fatty acid binding protein (L-FABP). In this report we address the question whether pristanic acid also acts as activator of PPARα and thus mediates the expression of its catabolizing enzymes. In a first in vivo approach we fed pristanic acid for 14 days to wildtype mice and to mice lacking sterol carrier protein 2/sterol carrier protein x which Ieads to a phenotype having high concentrations of branched-chain fatty acids. In either genotype, feeding pristanic acid was associated with a strong induction of peroxisomal β-oxidation enzymes tested (acyl-CoA oxidase, bifunctional enzyme, thiolase) as well as of L-FABP. The link between pristanic acid and protein expression observed was established by carrying out assays for transactivation of PPARα in transfected HepG2 cells. In comparison to hypolipidemic drugs and to straight-chain fatty acids known to be PPARα agonists, branched-chain phytanic and pristanic acids were substantially stronger activators, pristanic acid being even superior to phytanic acid.

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Stimulation of peroxisomal palmitoyl‐CoA oxidase activity by ciprofibrate in hepatic cell lines: Comparative studies in Fao, MH₁C₁ and HepG2 cells

Cited by 32 publications

References 27 publications

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Influence of Peroxisome Proliferators on Phosphoprotein Levels in Human and Rat Hepatic-Derived Cell Lines

Pristanic acid is activator of peroxisome proliferator activated receptor alpha

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Stimulation of peroxisomal palmitoyl‐CoA oxidase activity by ciprofibrate in hepatic cell lines: Comparative studies in Fao, MH1C1 and HepG2 cells

Cited by 32 publications

References 27 publications

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Influence of Peroxisome Proliferators on Phosphoprotein Levels in Human and Rat Hepatic-Derived Cell Lines

Pristanic acid is activator of peroxisome proliferator activated receptor alpha

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Stimulation of peroxisomal palmitoyl‐CoA oxidase activity by ciprofibrate in hepatic cell lines: Comparative studies in Fao, MH₁C₁ and HepG2 cells