Regulation of Membrane Fluidity by Lipid Desaturases

Kates, M.; Pugh, E.L.; Ferrante, Giulio

doi:10.1007/978-1-4684-4667-8_12

Cited by 48 publications

(31 citation statements)

References 56 publications

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“…The two resistant strains contained higher proportions of phosphatidylcholine and diphosphatidylglycerol compared with C. albicans A, but otherwise the differences in the relative amounts of each phospholipid between imidazole-sensitive and imidazole-resistant strains were complex and did not follow a pattern. The differences in fatty acid composition between phosphatidylcholine and its metabolic precursor phosphatidylethanolamine may indicate that phosphatidylcholine is a better substrate than phosphatidylethanolamine for 'palmitate desaturase', assuming that phospholipid is the substrate for desaturation in C. albicans as in other yeasts (Kates et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

The Lipid Composition of Azole-sensitive and Azole-resistant Strains of Candida albicans

Hitchcock¹,

Barrett‐Bee²,

Russell³

1986

Microbiology

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The lipid compositions of two azole-sensitive (A and B2630) and two azole-resistant (AD and KB) strains of the opportunistic fungal pathogen Candida albicans were studied by using several lipid extraction procedures: no differences were observed between the lipid content or total phospholipid/neutral lipid ratios of the four strains. All contained phosphatidylethanolamine, phosp hatidylc holine, phosphatid ylinosi to1 and p hosp hat id ylserine as major phospholipids, with smaller amounts of phosphatidylglycerol and diphosphatidylglycerol ; the relative proportions of these lipids differed between all four strains. The fatty acid composition of each major phospholipid within each strain differed, and there were also interstrain differences. A marked effect of culture growth phase in batch culture on lipid composition was observed. The major neutral lipids in each strain were triacylglycerol, non-esterified sterol and non-esterified fatty acid. The fatty acid compositions of the three fatty-acid-containing neutral lipids were distinct from each other and the phospholipids, and there were also interstrain differences. All strains possessed (1yso)phospholipase activity, which was nonspecific. The proportions of triacylglycerol and non-esterified fatty acid did not vary between strains, but the azole-resistant strains AD and KB contained more non-esterified sterol, giving them a phospholipid/sterol ratio approximately half that of azole-sensitive strains. There appeared to be a relationship between the phospholipid/sterol ratio of exponentially growing sensitive strains and their ability to take up azole; this did not extend to the resistant strains, which either did not take up azole (AD and KB) or took it up at a faster rate (Darlington) than sensitive strains. INTRODUCTIONCandida albicans is a widespread and troublesome opportunistic pathogen that causes a variety of superficial and deep-seated mycoses (Odds, 1979). Of the relatively few antifungal antibiotics available, those most commonly used to treat candidosis are the polyenes and the more recently introduced imidazoles (Speller, 1980). Polyenes work by complexing with membrane sterols (Hamilton-Miller, 1973). The primary action of imidazoles is probably inhibition of ergosterol synthesis that leads to an accumulation of 14a-methyl sterols which disrupt membrane structure and function (Van den Bossche et ul., 1982, 1983). However, imidazole actions are complex: they also inhibit a number of other yeast (and mammalian) membrane-bound enzymes (Uno et al., Mason et al., 1985), and at higher concentrations some of them affect yeast membranes by direct interaction with lipids (Cope, 1980; Brasseur et al., 1983).Clinical isolates of C. albicans vary considerably in their sensitivities to imidazoles (e.g. see Ryley et al., 1984), and azole-resistant strains have been isolated (Holt & Azmi, 1978 ;Horsburgh & Kirkpatrick, 1983; Warnock et al., 1983). The failure of two of these resistant strains (AD and , 1984). This might be due to an altered membrane lipid compos...

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Section: Discussionmentioning

confidence: 99%

The Lipid Composition of Azole-sensitive and Azole-resistant Strains of Candida albicans

Hitchcock¹,

Barrett‐Bee²,

Russell³

1986

Microbiology

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“…The unsaturation of fatty acids in membrane lipids might activate the Na ϩ /H ϩ antiport system via enhanced fluidity of the membrane with resultant protection of PSII and PSI activities. The activities of several membrane-bound enzymes are known to be affected by changes in membrane fluidity (Kates et al, 1984;Kamada et al, 1995). (d) The unsaturation of fatty acids might stimulate the synthesis of the Na ϩ /H ϩ antiporter(s) and/or H ϩ -ATPase(s).…”

Section: Possible Sites Affected By the Unsaturation Of Fatty Acids Imentioning

confidence: 99%

Unsaturated Fatty Acids in Membrane Lipids Protect the Photosynthetic Machinery against Salt-Induced Damage inSynechococcus

et al. 2001

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In this study, the tolerance to salt stress of the photosynthetic machinery was examined in relation to the effects of the genetic enhancement of the unsaturation of fatty acids in membrane lipids in wild-type and desA ϩ cells of Synechococcus sp. PCC 7942. Wild-type cells synthesized saturated and mono-unsaturated fatty acids, whereas desA ϩ cells, which had been transformed with the desA gene for the ⌬12 acyl-lipid desaturase of Synechocystis sp. PCC 6803, also synthesized diunsaturated fatty acids. Incubation of wild-type and desA ϩ cells with 0.5 m NaCl resulted in the rapid loss of the activities of photosystem I, photosystem II, and the Na ϩ /H ϩ antiport system both in light and in darkness. However, desA ϩ cells were more tolerant to salt stress and osmotic stress than the wild-type cells. The extent of the recovery of the various photosynthetic activities from the effects of 0.5 m NaCl was much greater in desA ϩ cells than in wild-type cells. The photosystem II activity of thylakoid membranes from desA ϩ cells was more resistant to 0.5 m NaCl than that of membranes from wild-type cells. These results demonstrated that the genetically engineered increase in unsaturation of fatty acids in membrane lipids significantly enhanced the tolerance of the photosynthetic machinery to salt stress. The enhanced tolerance was due both to the increased resistance of the photosynthetic machinery to the salt-induced damage and to the increased ability of desA ϩ cells to repair the photosynthetic and Na ϩ /H ϩ antiport systems.Salt stress is one of the main environmental factors that limit the growth and productivity of plants and micro-organisms. We have been investigating the mechanisms of the hyperosmotic stress-induced and the salt stress-induced inactivation of the photosynthetic machinery, focussing on the oxygen-evolving machinery of the photosystem II complex, which is the system that is most susceptible to such environmental stress in Synechococcus sp. PCC 7942 (hereafter Synechococcus; Allakhverdiev et al., 2000aAllakhverdiev et al., , 2000b. Hyperosmotic stress due to 1.0 m sorbitol induces the efflux of water through water channels and reduces the volume of cells by more than 50%. This loss of water from the cytosol might be expected to increase the intracellular concentration of salts, and it leads to the rapid but reversible inactivation of the oxygenevolving machinery (Allakhverdiev et al., 2000b).Salt stress due to 0.5 m NaCl has both osmotic and ionic effects (Allakhverdiev et al., 2000a). The osmotic effect due to 0.5 m NaCl is not as strong as the effect of 1.0 m sorbitol and inactivates reversibly the oxygen-evolving machinery. The ionic effect of 0.5 m NaCl is caused by the influx of Na ϩ ions through K ϩ (Na ϩ ) channels and the resultant increase in the intracellular concentration of Na ϩ ions and counterpart anions that are mostly Cl Ϫ ions (Allakhverdiev et al., 2000a). These changes result in the irreversible inactivation of the oxygen-evolving machinery. As a consequence salt stress appears t...

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“…Oleic and palmitoleic acids are the predominant unsaturated fatty acids present in fat depots and membrane phospholipids (2). The ratio of saturated to unsaturated fatty acids is thought to control the structural integrity and fluidity of membranes, which in turn modulate cell growth and differentiation (3,4). The regulation of SCD is of physiological importance because any changes in its activity can modulate the membrane fluidity and thereby alter cellular functions.…”

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confidence: 99%

Transforming Growth Factor-β Regulates Stearoyl Coenzyme A Desaturase Expression through a Smad Signaling Pathway

Samuel¹,

Nagineni²,

Kutty³

et al. 2002

Journal of Biological Chemistry

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The regulation of stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the synthesis of unsaturated fatty acids, is physiologically important because the ratio of saturated to unsaturated fatty acids is thought to control cellular functions by modulating the structural integrity and fluidity of cell membranes. Transforming growth factor-␤ (TGF-␤), a multifunctional cytokine, increased SCD mRNA expression in cultured human retinal pigment epithelial cells. This response was elicited by all three TGF-␤ isoforms, ␤1, ␤2, and ␤3. However, SCD mRNA expression was not increased either by other members of the TGF-␤ family or by other growth factors or cytokines. TGF-␤ also increased SCD mRNA expression in several other cell lines tested. The increase in SCD mRNA expression was preceded by a marked increase in Smad2 phosphorylation in TGF-␤-treated human retinal pigment epithelial cells. TGF-␤ did not induce SCD mRNA expression in a Smad4-deficient cell line. However, Smad4 overexpression restored the TGF-␤ effect in this cell line. Moreover, TGF-␤-induced SCD mRNA expression was effectively blocked by the overexpression of Smad7, an inhibitory Smad. Thus, a TGF-␤ signal transduction pathway involving Smad proteins appears to regulate the cellular expression of the SCD gene, and this regulation may play an important role in lipid metabolism.

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Regulation of Membrane Fluidity by Lipid Desaturases

Cited by 48 publications

References 56 publications

The Lipid Composition of Azole-sensitive and Azole-resistant Strains of Candida albicans

The Lipid Composition of Azole-sensitive and Azole-resistant Strains of Candida albicans

Unsaturated Fatty Acids in Membrane Lipids Protect the Photosynthetic Machinery against Salt-Induced Damage inSynechococcus

Transforming Growth Factor-β Regulates Stearoyl Coenzyme A Desaturase Expression through a Smad Signaling Pathway

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