Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes

Olivier, Lisa M.; Krisans, Skaidrite K.

doi:10.1016/s1388-1981(00)00139-6

Cited by 74 publications

(59 citation statements)

References 84 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: 46%

“…Cells quenched in low melting agarose were cut into approximately 1 mm 3 and post-fixed in reduced 1% osmium tetroxide for 1 h at room temperature. The cells were then dehydrated through a graded ethanol series (50,70,80, 90, 100%) for 15 min each, and embedded in Epon 812. Epoxy resin was polymerized for 24 h at 60°C.…”

Section: Culture Of Trophoblast Cells and Drug Treatmentmentioning

confidence: 99%

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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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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: 46%

Section: Culture Of Trophoblast Cells and Drug Treatmentmentioning

confidence: 99%

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Hashimoto

Shimooka

Iwasaki

et al. 2008

Biological & Pharmaceutical Bulletin

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“…38 On closer examination of the primary sequence of vHL, we identified a potential 100% canonical PTS2 import sequence in the N-terminal end of the middle of the molecule, making this PTS site the most potentially active among the protein sequences we compared. Furthermore, even if a protein's sequence is not 100% identical to the canonical PTS sites, other enzymes have been described that target to the peroxisome with similar, but nonconventional PTS sequences; these include acetoacetyl-CoA thiolase, 39 alanine:glyoxylate aminotransferase, 40 isopentenyl diphosphate dimethylallyl diphosphate isomerase, 41 and iNOS. 27,42 In fact, very large protein oligomers lacking PTS motifs have been shown to piggy-back onto other conventional peroxisomal proteins and gain entry into the peroxisomal matrix in their native three-dimensional configuration.…”

Section: Discussionmentioning

confidence: 99%

Peroxisomal Localization of Hypoxia-Inducible Factors and Hypoxia-Inducible Factor Regulatory Hydroxylases in Primary Rat Hepatocytes Exposed to Hypoxia-Reoxygenation

Khan

Michalopoulos

Stolz

2006

The American Journal of Pathology

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Many signals involved in pathophysiology are controlled by hypoxia-inducible factors (HIFs), transcription factors that induce expression of hypoxiaresponsive genes. HIFs are post-translationally regulated by a family of O 2 -dependent HIF hydroxylases: four prolyl 4-hydroxylases and an asparaginyl hydroxylase. Most of these enzymes are abundant in resting liver, which is itself unique because of its physiological O 2 gradient, and they can exist in both nuclear and cytoplasmic pools. In this study, we analyzed the cellular localization of endogenous HIFs and their regulatory hydroxylases in primary rat hepatocytes cultured under hypoxia-reoxygenation conditions. In hepatocytes, hypoxia targeted HIF-1␣ to the peroxisome, rather than the nucleus, where it co-localized with von Hippel-Lindau tumor suppressor protein and the HIF hydroxylases. Confocal immunofluorescence microscopy demonstrated that the HIF hydroxylases translocated from the nucleus to the cytoplasm in response to hypoxia, with increased accumulation in peroxisomes on reoxygenation. These results were confirmed via immunotransmission electron microscopy and Western blotting. Surprisingly, in resting liver tissue, perivenous localization of the HIF hydroxylases was observed, consistent with areas of low pO 2 . In conclusion, these studies establish the peroxisome as a highly relevant site of subcellular localization and function for the endogenous HIF pathway in

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“…Recently, it has been demonstrated by other groups that peroxisomes contain a number of enzymes involved in cholesterol biosynthesis, which were previously considered to be cytosolic, or located exclusively in the endoplasmic reticulum (ER). Peroxisomes have been shown to contain acetoacetyl-coenzyme A (CoA) thiolase, 1,2) 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase, 3) HMG-CoA reductase, 4,5) mevalonate kinase (MVK), 6,7) phosphomevalonate kinase (PMVK), 8) MPD, 8) isopentenyl pyrophosphate isomerase (IPPase), 9) and farnesyl pyrophosphate synthase (FPPase). 10) Recent data have also shown that the activity of some enzymes, including MVK and FPPase, is significantly reduced in liver tissue obtained from patients with peroxisomedeficient diseases (Zellweger syndrome and neonatal adrenoleukodystrophy), thus indicating the peroxisomal localization of these enzymes.…”

Section: Introductionmentioning

confidence: 99%

Mevalonate Pyrophosphate Decarboxylase is Predominantly Located in the Cytosol of both B16 and B16F10 Cells in Mouse Melanoma Treated with Lovastatin

Michihara

Morita

Toda

et al. 2008

JOURNAL OF HEALTH SCIENCE

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Recently, it has been questioned whether mevalonate pyrophosphate decarboxylase (MPD) is predominantly located in the peroxisomes or cytosol. We previously reported that a small amount of MPD in the liver of rats fed a CP diet (5% cholestyramine and 0.1% pravastatin) existed in the peroxisomes, although MPD is predominantly located in the cytosol in the liver of rats fed normal chow and a CP diet for 12 days. In the present study, we examined the subcellular distribution of MPD in mouse melanoma cells (B16 and B16F10) treated with or without lovastatin, using digitonin permeabilization and immunoblotting. In permeabilized B16 by digitonin after treatment with or without lovastatin, 95% and 5%, or 98% and 2% of MPD existed in the cytosol and membrane/organelle (M/O) fraction, respectively. Using B16F10 under the same conditions, 80% and 20%, or 91% and 9% of MPD existed in the cytosol and M/O fraction, respectively. These results indicated that MPD was predominantly located in the cytosol in both mouse melanoma cells treated with or without lovastatin.

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Peroxisomal protein targeting and identification of peroxisomal targeting signals in cholesterol biosynthetic enzymes

Cited by 74 publications

References 84 publications

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Presence and Some Characteristics of Peroxisomes in Immortalized Human Trophoblast Cells

Peroxisomal Localization of Hypoxia-Inducible Factors and Hypoxia-Inducible Factor Regulatory Hydroxylases in Primary Rat Hepatocytes Exposed to Hypoxia-Reoxygenation

Mevalonate Pyrophosphate Decarboxylase is Predominantly Located in the Cytosol of both B16 and B16F10 Cells in Mouse Melanoma Treated with Lovastatin

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