Diversity in the Ability of Cultured Cells to Elongate and Desaturate Essential (n‐6 and n‐3) Fatty Acidsa

Grammatikos, Stephanos I.; Subbaiah, Papasani V.; Victor, Thomas A.; Miller, William M.

doi:10.1111/j.1749-6632.1994.tb44366.x

Cited by 29 publications

(18 citation statements)

References 39 publications

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“…The ability of different types of cells to elongate and desaturate n-6 and n-3 fatty acids is diverse (Grammatikos et al 1994b). However, these enzymes have been shown to be expressed in cumulus cells, and are involved in follicular growth and oocyte competence in rat (Moreau et al 2006), human (Feuerstein et al 2007) and zebrafish (Ishak et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Impact of linoleic acid on bovine oocyte maturation and embryo development

Marei¹,

Wathes²,

2010

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Linoleic acid (LA; 18:2 n-6) is the most abundant fatty acid in bovine follicular fluid, and it was previously reported that LA concentration significantly decreases when follicle size increases. This suggests that LA may have a role in the regulation of oocyte maturation. The present study investigated the effect of LA supplementation on bovine oocyte maturation and early embryo development in vitro. Treatment of cumulus-oocyte complexes (COCs) with LA significantly inhibited cumulus cell expansion and retarded development of the oocytes to the metaphase II (MII) stage in a dose-dependent manner. This effect was reversible, and the oocytes developed to the MII stage after extended culture in the absence of LA. Treatment of COCs with LA also resulted in a significantly lower percentage of cleaved embryos and blastocyst yield. Furthermore, COCs treated with LA had significant effects compared with controls in i) increasing prostaglandin E 2 concentration in the medium, ii) decreasing intracellular cAMP at 6 and 24 h of maturation and iii) decreasing phosphorylation of the MAPK1 and 3 at 24 h, and AKT at 6 h of maturation. In conclusion, LA supplementation to bovine oocytes during maturation altered the molecular mechanisms regulating oocyte maturation and resulted in decreased percentage of oocytes at MII stage and inhibition of the subsequent early embryo development. These data provide evidence for adverse effects of LA on oocyte development, which can be associated with dietary increased level of LA in the follicular fluid and the decline in fertility in farm animals and human.Reproduction (2010) 139 979-988

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Section: Discussionmentioning

confidence: 99%

Impact of linoleic acid on bovine oocyte maturation and embryo development

Marei¹,

Wathes²,

2010

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“…Indeed, 18:2 FA is a poor substrate for the elongation/ desaturation machinery in endothelial cells ( 50,51 ).…”

Section: Discussionmentioning

confidence: 99%

Acyl chain-dependent effect of lysophosphatidylcholine on endothelial prostacyclin production

Riederer

Ojala

Hrzenjak

et al. 2010

Journal of Lipid Research

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“…acyl transferase) steps. The reason for this defect has been suggested to be due to extensive chromosomal deletions, but no molecular evidence is available [11], [12]. The Δ8-desaturation substrates 20∶2n−6 and 20∶3n−3 are often detected, thus suggesting that the elongation step is functional [12], [13].…”

Section: Introductionmentioning

confidence: 99%

“…The reason for this defect has been suggested to be due to extensive chromosomal deletions, but no molecular evidence is available [11], [12]. The Δ8-desaturation substrates 20∶2n−6 and 20∶3n−3 are often detected, thus suggesting that the elongation step is functional [12], [13]. Until recently, the Δ8-desaturation substrates 20∶2n−6 and 20∶3n−3 were widely considered dead-end products, even though they are found in human plasma and red cells as well as other tissues.…”

Section: Introductionmentioning

confidence: 99%

FADS2 Function Loss at the Cancer Hotspot 11q13 Locus Diverts Lipid Signaling Precursor Synthesis to Unusual Eicosanoid Fatty Acids

et al. 2011

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BackgroundGenes coding for the fatty acid desaturases (FADS1, 2, 3) localized at the cancer genomic hotspot 11q13 locus are required for the biosynthesis of 20 carbon polyunsaturated fatty acids (PUFA) that are direct eicosanoid precursors. In several cancer cell lines, FADS2 encoded Δ6 and Δ8 desaturation is not functional.Methodology/Principal FindingsAnalyzing MCF7 cell fatty acids with detailed structural mass spectrometry, we show that in the absence of FADS2 activity, the FADS1 product Δ5-desaturase operates to produce 5,11,14–20∶3 and 5,11,14,17–20∶4. These PUFA are missing the 8–9 double bond of the eicosanoid signaling precursors arachidonic acid (5,8,11,14–20∶4) and eicosapentaenoic acid (5,8,11,14,17–20∶5). Heterologous expression of FADS2 restores Δ6 and Δ8-desaturase activity and normal eicosanoid precursor synthesis.Conclusions/SignificanceThe loss of FADS2-encoded activities in cancer cells shuts down normal PUFA biosynthesis, deleting the endogenous supply of eicosanoid and downstream docosanoid precursors, and replacing them with unusual butylene-interrupted fatty acids. If recapitulated in vivo, the normal eicosanoid and docosanoid cell signaling milieu would be depleted and altered due to reduction and substitution of normal substrates with unusual substrates, with unpredictable consequences for cellular communication.

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Diversity in the Ability of Cultured Cells to Elongate and Desaturate Essential (n‐6 and n‐3) Fatty Acids^a

Cited by 29 publications

References 39 publications

Impact of linoleic acid on bovine oocyte maturation and embryo development

Impact of linoleic acid on bovine oocyte maturation and embryo development

Acyl chain-dependent effect of lysophosphatidylcholine on endothelial prostacyclin production

FADS2 Function Loss at the Cancer Hotspot 11q13 Locus Diverts Lipid Signaling Precursor Synthesis to Unusual Eicosanoid Fatty Acids

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