Phytosphingosine groups as quantitatively significant components of the sphingolipids of the mucosa of the small intestines of some mammalian species

Okabe, Keisuke; Keenan, Roy W.; Schmidt, Gerhard

doi:10.1016/0006-291x(68)90043-0

Cited by 60 publications

(26 citation statements)

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“…2). In mammals, PHS is localized to specific tissues such as the skin and the small intestine 7,[12][13][14] . Consistent with the abundance of PHS in the skin, odd-numbered Cers also exist in the skin at extremely high levels 4 , suggesting that PHS may be the major source of odd-numbered FAs in PHS-rich mammalian tissues.…”

Section: Discussionmentioning

confidence: 99%

“…The saturated LCB dihydrosphingosine (DHS) also exists throughout the body, although the levels of DHS are less abundant than those of sphingosine 6 . Phytosphingosine (PHS), which contains a hydroxyl group at the C4 position, is localized to specific tissues such as the skin and small intestine 7,[12][13][14] . PHS is a major LCB in yeast, and it also exists in plants 15 .…”

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Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids

et al. 2014

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The long-chain base phytosphingosine is a component of sphingolipids and exists in yeast, plants and some mammalian tissues. Phytosphingosine is unique in that it possesses an additional hydroxyl group compared with other long-chain bases. However, its metabolism is unknown. Here we show that phytosphingosine is metabolized to odd-numbered fatty acids and is incorporated into glycerophospholipids both in yeast and mammalian cells. Disruption of the yeast gene encoding long-chain base 1-phosphate lyase, which catalyzes the committed step in the metabolism of phytosphingosine to glycerophospholipids, causes an B40% reduction in the level of phosphatidylcholines that contain a C15 fatty acid. We also find that 2-hydroxypalmitic acid is an intermediate of the phytosphingosine metabolic pathway. Furthermore, we show that the yeast MPO1 gene, whose product belongs to a large, conserved protein family of unknown function, is involved in phytosphingosine metabolism. Our findings provide insights into fatty acid diversity and identify a pathway by which hydroxyl group-containing lipids are metabolized.

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Section: Discussionmentioning

confidence: 99%

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Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids

et al. 2014

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“…In contrast to sphingosine-conjugated ceramides, dihydroceramides (which contain dihydrosphingosine) do not induce apoptosis ( 6,(48)(49)(50). Phytosphingosine-based sphingolipids are also observed in skin, intestine, and kidney (51)(52)(53). Although the importance of phyto-type sphingolipids in these cells is recognized ( 54, 55 ) (e.g., synthetic phytoceramides are more cytotoxic than ceramides ( 56 )), the precise role of the lipids remains unsolved.…”

Section: Resultsmentioning

confidence: 99%

Multiplex analysis of sphingolipids using amine-reactive tags (iTRAQ)

Nabetani

Makino

Hullin-Matsuda

et al. 2011

Journal of Lipid Research

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This article is available online at http://www.jlr.orgCeramides are central intermediates of sphingolipid biosynthesis and degradation ( 1,2 ). In addition to their metabolic importance, ceramides play a crucial role in a variety of signaling events, including differentiation ( 3 ), senescence ( 4 ), proliferation ( 5 ), and apoptosis ( 6, 7 ). Due to their physiological importance, analysis of their generation as well as their quantifi cation has received considerable attention. Ceramides are quantitatively relatively minor cellular lipid components; thus, highly sensitive detection is required for quantifi cation. Several methods of quantifying ceramide have been reported, including gas chromatography (GC) ( 8 ), high-performance liquid chromatography (HPLC) ( 9-11 ), diacylglycerol kinase assay ( 12 ), and mass spectrometry (MS) ( 13-18 ). Recent advances in MS have made this method a promising approach to the quantitative measurement of ceramides and other lipids. Considering the low cellular concentration of ceramides, it is important to concurrently determine the concentration ratios of ceramides from different samples, such as before and after stimulation of cells. However, simultaneous analysis of ceramide levels across multiple samples has not been reported to date.Isobaric tags for relative and absolute quantitation (iTRAQ) have been developed to compare the protein expression levels in multiple samples ( 19,20 ). These reagents have identical overall mass but vary in terms of the distribution of heavy carbon, nitrogen, and oxygen isotopes within their structure. One big advantage of iTRAQ is enhanced sensitivity because the intensity of the peaks Abstract Ceramides play a crucial role in divergent signaling events, including differentiation, senescence, proliferation, and apoptosis. Ceramides are a minor lipid component in terms of content; thus, highly sensitive detection is required for accurate quantifi cation. The recently developed isobaric tags for relative and absolute quantitation (iTRAQ) method enables a precise comparison of both protein and aminophospholipids. However, iTRAQ tagging had not been applied to the determination of sphingolipids. 31 March 2011. Published, JLR Papers in Press, April 11, 2011 DOI 10.1194 Multiplex analysis of sphingolipids using amine-reactive tags (iTRAQ) Abbreviations: MDCK, Madin Darby canine kidney; MRM, multiple reaction monitoring; PPS, 3-[3-(1,1-bisalkyloxyethyl)pyridine-1-yl] propane-1-sulfonate; SCDase, sphingolipid ceramide N -deacylase; SMase, sphingomyelinase; iTRAQ, isobaric tags for relative and absolute quantitation. Manuscript received 7 February 2011 and in revised form

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“…The major type of sphingoid base, Sph, has a double bond between C4 and C5 position, whereas DHS is saturated at that site (Figure 1). Phytosphingosine (PHS), which has hydroxyl group at the C4 position, exists in certain tissues, in particular the intestine, kidney and epidermis of mammals [9-11]. All sphingolipid analogs that activated PPARs [5] had a PHS-based structure.…”

Section: Introductionmentioning

confidence: 99%

Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors

et al. 2011

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BackgroundPeroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate lipid and glucose metabolism. PPARα is highly expressed in the liver and controls genes involved in lipid catabolism. We previously reported that synthetic sphingolipid analogs, part of which contains shorter-length fatty acid chains than natural sphingolipids, stimulated the transcriptional activities of PPARs. Sphingosine and dihydrosphingosine (DHS) are abundant sphingoid bases, and ceramide and dihydroceramide are major ceramide species in mammals. In contrast, phytosphingosine (PHS) and DHS are the main sphingoid bases in fungi. PHS and phytoceramide exist in particular tissues such as the epidermis in mammals, and involvement of ceramide species in PPARβ activation in cultured keratinocytes has been reported. The purpose of the present study is to investigate whether natural sphingolipids with C18 fatty acid and yeast-derived sphingoid bases activate PPARs as PPAR agonists.MethodLipids of brewer's yeast contain PHS- and DHS-based sphingolipids. To obtain the sphingoid bases, lipids were extracted from brewer's yeast and acid-hydrolyzed. The sphingoid base fraction was purified and quantified. To assess the effects of sphingolipids on PPAR activation, luciferase reporter assay was carried out. NIH/3T3 and human hepatoma (HepG2) cells were transfected with expression vectors for PPARs and retinoid × receptors, and PPAR responsive element reporter vector. When indicated, the PPAR/Gal4 chimera system was performed to enhance the credibility of experiments. Sphingolipids were added to the cells and the dual luciferase reporter assay was performed to determine the transcriptional activity of PPARs.ResultsWe observed that phytoceramide increased the transcriptional activities of PPARs significantly, whereas ceramide and dihydroceramide did not change PPAR activities. Phytoceramide also increased transactivation of PPAR/Gal4 chimera receptors. Yeast-derived sphingoid base fraction, which contained PHS and DHS, or authentic PHS or DHS increased PPAR-dependent transcription. Additionally, phytoceramide stimulated PPARα activity in HepG2 hepatocytes, suggesting that phytoceramide activates genes regulated by PPARα.ConclusionsPhytoceramide and yeast-derived sphingoid bases activate PPARs, whereas ceramide and dihydroceramide do not change the PPAR activity. The present findings suggest that phytoceramide acts as a PPAR ligand that would regulate PPAR-targeted genes.

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Phytosphingosine groups as quantitatively significant components of the sphingolipids of the mucosa of the small intestines of some mammalian species

Cited by 60 publications

References 13 publications

Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids

Identification of the phytosphingosine metabolic pathway leading to odd-numbered fatty acids

Multiplex analysis of sphingolipids using amine-reactive tags (iTRAQ)

Phytoceramide and sphingoid bases derived from brewer's yeast Saccharomyces pastorianus activate peroxisome proliferator-activated receptors

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