Sterol Synergism in Paramecium tetraurelia

Whitaker, Bruce D.; Nelson, David Lee

doi:10.1099/00221287-134-6-1441

Cited by 12 publications

(25 citation statements)

References 16 publications

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“…Ergosterol, a fungal sterol, may sustain animal cell growth, provided that suboptimal amounts of cholesterol are also available (27,28). Similar results were obtained with the combination of other sterols in different organisms (29)(30)(31). The existing sterol synergism indicates that low concentrations of the natural sterol, which are insufficient to substantially sustain cell growth per se, elicit synergistic effects when added in combination with another sterol (27,32,33).…”

supporting

confidence: 71%

“…These studies led to the postulation of a regulatory role for sterols during cell growth, which appears to be highly specific and fulfilled by very low levels of the natural sterol. In contrast, the bulk membrane function, which accounts for the major amount of the sterol in the cell, is potentially accomplished by different sterols with broad specificity (27,(29)(30)(31).…”

mentioning

confidence: 99%

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Effects of distal cholesterol biosynthesis inhibitors on cell proliferation and cell cycle progression

Fernández

Martín

Gómez-Coronado

et al. 2005

Journal of Lipid Research

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supporting

confidence: 71%

mentioning

confidence: 99%

Effects of distal cholesterol biosynthesis inhibitors on cell proliferation and cell cycle progression

Fernández

Martín

Gómez-Coronado

et al. 2005

Journal of Lipid Research

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“…Analysis of cellular free sterol levels and plasma membrane properties suggested that sterols such as cholesterol and dihydrocholesterol satisfy a bulk membrane requirement, whereas ergosterol serves a highly specific function (35). A similar phenomenon was observed in the natural auxotroph Paramecium tetraurelia, which has an absolute requirement for one of a small group of structurally related phytosterols including stigmasterol, ␤-sitosterol, and poriferasterol (37). Stigmasterol at levels as low as 20 ng͞ml supports growth if a second relatively nonspecific sterol is provided at higher concentrations (1 g͞ml).…”

Section: Discussionmentioning

confidence: 78%

“…These findings were taken to indicate that sterols play more than one role in membranes. Later, sterol synergism was demonstrated in unicellular eukaryotes including yeast (36) and Paramecium (37). Yeast mutants that require exogenous sterols can grow in a variety of sterols if trace amounts of ergosterol are present.…”

Section: Discussionmentioning

confidence: 99%

Dual roles for cholesterol in mammalian cells

Rychnovsky

Belani

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

124

103

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The structural features of sterols required to support mammalian cell growth have not been fully defined. Here, we use mutant CHO cells that synthesize only small amounts of cholesterol to test the capacity of various sterols to support growth. Sterols with minor modifications of the side chain (e.g., campesterol, ␤-sitosterol, and desmosterol) supported long-term growth of mutant cells, but sterols with more complex modifications of the side chain, the sterol nucleus, or the 3-hydroxy group did not. After 60 days in culture, the exogenous sterol comprised >90% of cellular sterols. Inactivation of residual endogenous synthesis with the squalene epoxidase inhibitor NB-598 prevented growth in ␤-sitosterol and greatly reduced growth in campesterol. Growth of cells cultured in ␤-sitosterol and NB-598 was restored by adding small amounts of cholesterol to the medium. Surprisingly, enantiomeric cholesterol also supported cell growth, even in the presence of NB-598. Thus, sterols fulfill two roles in mammalian cells: (i) a bulk membrane requirement in which phytosterols can substitute for cholesterol and (ii) other processes that specifically require small amounts of cholesterol but are not enantioselective.ent-cholesterol ͉ phytosterols ͉ NB-598 S terols are essential components of eukaryote membranes. Their incorporation enhances the packing of the acyl chains of phospholipids in the hydrophobic phase of the bilayer, increases its mechanical strength, and reduces its permeability (1). Despite this crucial role, most animal species (e.g., nematodes and arthropods) cannot make sterols and so must get them from the diet. Vertebrates, by contrast, make sterols de novo from acetyl-coenzyme A and so do not require exogenous sterols. Accordingly, studies to probe sterol requirements of eukaryotes have used in invertebrates (2, 3), protazoans (4, 5), or yeast strains defective in sterol synthesis (6-8), so that the sterol composition of the organism can be controlled exogenously.Although phytosterols can account for a substantial portion of total dietary sterols (approximately one-third in humans), vertebrates systematically exclude them from the body. Cholesterol predominates in the membranes of most animals and is virtually the exclusive sterol of vertebrates. Invertebrates such as insects typically convert phytosterols to cholesterol by dealkylating C24 in the side chain, thereby furnishing cholesterol needed by membranes and preventing accumulation of noncholesterol sterols. Mammals and other vertebrates can either make sterols de novo or get cholesterol from the diet. Accumulation of other dietary sterols in these animals is prevented by the action of two ATP-binding cassette transporters, ABCG5 and ABCG8 (9), which function as a heterodimer to limit intestinal absorption and facilitate biliary excretion of noncholesterol sterols (10, 11). Thus, cholesterol comprises the great majority of vertebrate sterols, even in animals ingesting large quantities of phytosterols.The biological basis for selection of cholesterol as t...

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“…Cells from cultures with added sterols were collected by centrifugation at 3,000 ϫ g for 5 min at 4°C and extracted with 5 ml hexane, after a UP 607 and DW 607 are the upstream and downstream regions from the TTHERM_00438800 putative gene. neo3 is the cassette from the plasmid pBS-MnB-3 (38). WT 607 allele and KO 607 allele are the sequences amplified to check the replacement of the endogenous gene in the KO607 mutant; TTHERM_438800 and ␣-tubulin sequences were amplified in the RNA expression analysis.…”

mentioning

confidence: 99%

A Novel Sterol Desaturase-Like Protein Promoting Dealkylation of Phytosterols in Tetrahymena thermophila

et al. 2011

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The gene TTHERM_00438800 (DES24) from the ciliate Tetrahymena thermophila encodes a protein with three conserved histidine clusters, typical of the fatty acid hydroxylase superfamily. Despite its high similarity to sterol desaturase-like enzymes, the phylogenetic analysis groups Des24p in a separate cluster more related to bacterial than to eukaryotic proteins, suggesting a possible horizontal gene transfer event. A somatic knockout of DES24 revealed that the gene encodes a protein, Des24p, which is involved in the dealkylation of phytosterols. Knocked-out mutants were unable to eliminate the C-24 ethyl group from C 29 sterols, whereas the ability to introduce other modifications, such as desaturations at positions C-5(6), C-7(8), and C-22(23), were not altered. Although C-24 dealkylations have been described in other organisms, such as insects, neither the enzymes nor the corresponding genes have been identified to date. Therefore, this is the first identification of a gene involved in sterol dealkylation. Moreover, the knockout mutant and wild-type strain differed significantly in growth and morphology only when cultivated with C 29 sterols; under this culture condition, a change from the typical pear-like shape to a round shape and an alteration in the regulation of tetrahymanol biosynthesis were observed. Sterol analysis upon culture with various substrates and inhibitors indicate that the removal of the C-24 ethyl group in Tetrahymena may proceed by a mechanism different from the one currently known.Sterols are lipophilic membrane components essential for the structural integrity of most eukaryotic cells. Together with phospholipids, they regulate the fluidity of the lipid bilayers and permeability barrier properties (4); they also serve as precursors of bile salts and a number of different steroid hormones in mammals, brassinosteroids in plants and fungi (2), and ecdysteroids in arthropods (14). Sterols are also actively involved in the modulation of cell signaling, in the transport and distribution of lipophilic molecules, and in the formation of lipid rafts (22).For most organisms in which sterols are de novo synthesized, such as vertebrates (cholesterol), plants (stigmasterol, ␤-sitosterol, and campesterol), and fungi (ergosterol), the enzymes involved have been well identified and characterized. Most of them can be grouped into four families of proteins: (i) the cytochrome b 5 (Cytb 5 )-dependent fatty acid hydroxylase superfamily, composed of C-5 sterol desaturases (erg3), C-4 sterol methyl oxidases (erg25), and cholesterol 25-hydroxylases; (ii) the S-adenosyl-L-methionine sterol methyltransferase (SMT) family, composed of the SMT1 and SMT2 types, which are typical in plants, and C-24 sterol methyltransferase, which has been described for fungi (erg6); (iii) the highly hydrophobic reductases, which include C-7, C-14, and C-24 sterol reductases; and (iv) the cytochrome P450 family, with C-22 sterol desaturases (erg5) and C-14 sterol demethylases (erg11) as its main representatives. Other eukaryotic org...

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Sterol Synergism in Paramecium tetraurelia

Cited by 12 publications

References 16 publications

Effects of distal cholesterol biosynthesis inhibitors on cell proliferation and cell cycle progression

Effects of distal cholesterol biosynthesis inhibitors on cell proliferation and cell cycle progression

Dual roles for cholesterol in mammalian cells

A Novel Sterol Desaturase-Like Protein Promoting Dealkylation of Phytosterols in Tetrahymena thermophila

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