Peroxisomes in adrenal steroidogenesis

Magalhães, M. M.; Magalhäes, Maria C.

doi:10.1002/(sici)1097-0029(19970315)36:6<493::aid-jemt6>3.0.co;2-j

Cited by 18 publications

(15 citation statements)

References 91 publications

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“…[32][33][34]48) It is reported that many data pointed out the important role of peroxisomes in steroidogenesis. [49][50][51] In the present study, clofibrate, rodent peroxisome proliferator may proliferate peroxisomes of human trophoblast cells to a lesser extent. Therefore, immortalized human trophoblast cells (TCL-1) seem to be useful for investigating the participation of microperoxisomes of human trophoblast cells in functions such as steroidgenesis.…”

Section: )supporting

confidence: 48%

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Hashimoto

Shimooka

Iwasaki

et al. 2008

Biological & Pharmaceutical Bulletin

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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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Section: )supporting

confidence: 48%

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Hashimoto

Shimooka

Iwasaki

et al. 2008

Biological & Pharmaceutical Bulletin

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“…35,36) We considered a possible mechanistic link between peroxisomes and progesterone synthesis as follows. Peroxisomes participate in fatty acid b-oxidation and the mevalonate pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Peroxisomes participate in fatty acid b-oxidation and the mevalonate pathway. 36,37) Acetyl-CoA derived from b-oxidation may be used for cholesterol synthesis in peroxisomes. Prognenolone is synthesized from cholesterol by cytochrome P450scc and is used for progesterone synthesis.…”

Section: Discussionmentioning

confidence: 99%

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

Hashimoto

Morita

Iwasaki

et al. 2009

Biological & Pharmaceutical Bulletin

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“…The adrenal cortex is a site of active steroidogenesis, and the covalent adduction of estrogen metabolites with DNA has been demonstrated experimentally (44). Additionally, steroidogenesis is associated with the potential for generating reactive oxygen species (45)(46)(47). This tissuespecific expression pattern of pol suggests a role in the response to DNA damage from reactive oxygen species and/or aromatic hydrocarbons.…”

Section: Discussionmentioning

confidence: 99%

Human DNA Polymerase κ Bypasses and Extends beyond Thymine Glycols during Translesion Synthesis in Vitro, Preferentially Incorporating Correct Nucleotides

Fischhaber

Gerlach

Feaver

et al. 2002

Journal of Biological Chemistry

104

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Human polymerase (pol), the product of the human POLK (DINB1) gene, is a member of the Y superfamily of DNA polymerases that support replicative bypass of chemically modified DNA bases (Ohmori, H., Friedberg, E. C., Fuchs, R. P., Goodman, M. F., Hanaoka, F., Hinkle, D., Kunkel, T. A., Lawrence, C. W., Livneh, Z., Nohmi, T., Prakash, L., Prakash, S., Todo, T., Walker, G. C., Wang, Z., and Woodgate, R. (2001) Mol. Cell 8, 7-8; Gerlach, V. L., Aravind, L., Gotway, G., Schultz, R. A., Koonin, E. V., and Friedberg, E. C. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 11922-11927). Pol is shown here to bypass 5,6-dihydro-5,6-dihydroxythymine (thymine glycol) generated in two different DNA substrate preparations. Pol inserts the correct base adenine opposite thymine glycol in preference to the other three bases. Additionally, the enzyme correctly extends beyond the site of the thymine glycol lesion when presented with adenine opposite thymine glycol at the primer terminus. However, steady state kinetic analysis of nucleotides incorporated opposite thymine glycol demonstrates different misincorporation rates for guanine with each of the two DNA substrates. The two substrates differ only in the relative proportions of thymine glycol stereoisomers, suggesting that pol distinguishes among stereoisomers and exhibits reduced discrimination between purines when incorporating a base opposite a 5R thymine glycol stereoisomer. When extending beyond the site of the lesion, the misincorporation rate of pol for each of the three incorrect nucleotides (adenine, guanine, and thymine) is dramatically increased. Our findings suggest a role for pol in both nonmutagenic and mutagenic bypass of oxidative damage.Many types of base damage in DNA cause structural modifications that can result in the stalling or complete arrest of high fidelity DNA synthesis during DNA replication (3, 4). However, the potential for cell death attendant on arrested DNA replication can be mitigated by a mechanism called translesion DNA synthesis (TLS) (5-7). This process effects the replicative bypass of sites of base damage, allowing high fidelity semiconservative DNA synthesis to continue. Important new insights into the biochemical mechanism of TLS have recently been gained by the discovery of a number of new DNA polymerases, all of which share the properties of limited fidelity and processivity when copying undamaged DNA, as well as a lack of 3Ј 3 5Ј proofreading exonuclease activity (1, 5-9). Multiple DNA polymerases of this class have been shown to support TLS of one or more types of base damage in vitro. In some instances, this role is supported by genetic or other biological evidence. Hence, a general theme is beginning to emerge that the redundancy for error-prone DNA polymerases in prokaryotic and especially in eukaryotic cells reflects a requirement for the bypass of multiple types of base damage that can arrest normal DNA replication (5). Recent structural studies on a number of these polymerases suggest that translesion synthesis is effected by a less ...

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Peroxisomes in adrenal steroidogenesis

Cited by 18 publications

References 91 publications

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

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

Human DNA Polymerase κ Bypasses and Extends beyond Thymine Glycols during Translesion Synthesis in Vitro, Preferentially Incorporating Correct Nucleotides

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