Disease relevance of Linoleate

• We tested the hypothesis that the mechanism of melatonin's anticancer action in vivo involves the inhibition of tumor LA uptake and metabolism to 13-HODE in hepatoma 7288CTC [1].
• In MDA-MB-231 cells, DADS antagonized the effect of linoleic acid (LA), a potent breast cancer cell stimulator (at DADS = 1.8 microM and LA > or = 6.5x10(2) microM concentration), and synergized the effect of eicosapentaenoic acid (EPA), a potent breast cancer cell suppressor (at DADS >3 x 10(-3) microM and EPA > 6.3 x 10(-1) microM concentration) [2].
• A decreased percentage of linoleic acid (LA) in triglycerides, of arachidonic acid (AA) in PC and of eicosapentaenoic acid (EPA) in triglycerides, FFA, PC and PE could be found in the kidneys of SHR at 8 weeks of age, i.e. during the development of hypertension [3].

High impact information on Linoleate

• Perfusion of tissue-isolated tumors in situ with melatonin (1 nM) rapidly and reversibly inhibited the uptake of plasma fatty acids (FAs), including LA, and its metabolism to 13-HODE [1].
• The inhibition of these signal transduction events by melatonin culminates in the suppression of LA uptake, LA metabolism to the mitogenic signaling molecule 13-HODE, and cancer growth [1].
• Growth of a yeast fox2sps19Delta mutant in which Fox2p was exchanged with rat peroxisomal multifunctional enzyme type 1 on trans-9,trans-12 linolelaidic acid medium gave credence to this theory [4].
• Val-349 and Ser-530, recently identified as important determinants for efficient oxygenation of DHLA by PGHS-1, play similar roles in the oxygenation of EPA and LA [5].
• Both EPA and LA bind in the active site with orientations similar to those seen previously with AA and dihomo-gamma-linolenic acid (DHLA) [5].

Chemical compound and disease context of Linoleate

• The growth of rat hepatoma 7288CTC in vivo is stimulated by the uptake of linoleic acid (LA) and its metabolism to 13-hydroxyoctadecadienoic acid (13-HODE), an important mitogenic signaling molecule within this tumor [1].
• Remarkably, omega-6 PUFAs linoleic acid (LA) and arachidonic acid (ARA), suppressors of both hepatic and adipocytic FAS-dependent lipogenesis, had no significant inhibitory effects on the activity of tumor-associated FAS in SK-Br3 breast cancer cells [6].
• In support of this hypothesis, light during darkness suppresses nocturnal melatonin production and stimulates the LA metabolism and growth of rat hepatoma and human breast cancer xenografts [7].

Biological context of Linoleate

• Interactions between LA and (n-3) fatty acids capable of regulating cell proliferation in solid tumors in vivo are not yet well defined [8].
• Linoleic acid (LA) and other fatty acids added to respiring durum wheat mitochondria (DWM) were found to cause a remarkable membrane potential (deltaPsi) decrease, as monitored by measuring safranin fluorescence [9].
• Our data suggest that octadecadienoic acids and diacylglycerol synergistically induce platelet activation via protein kinase C. Furthermore, linolelaidic acid may provide a useful experimental tool to study fatty acid regulation of protein kinase C in intact cells [10].
• Octadecadienoic acids (linoleic acid and linolelaidic acid) and the diacylglycerol, 1-oleoyl-2-acetyl-rac-glycerol (OAG) concentration-dependently induced activation of gel-filtered human platelets, i.e. aggregation and phosphorylation of 20 kDa and 47 kDa peptides [10].
• Fatty acid monolayers consisting of pure linoleic acid, linolelaidic acid, and oleic acid were autoxidized at 60 C. The rates of autoxidation of linoleic acid and linolelaidic acid monolayers followed by the disappearance of substrates are considerably faster than that in bulk phase, and the rates conform to apparent first order kinetics [11].

Anatomical context of Linoleate

• The effects of preformed dietary arachidonic acid (AA, 20:4n-6) on murine phospholipid fatty acid composition in tissues capable (liver) and incapable (peritoneal exudate cells, PEC) of desaturating and elongating linoleic acid (LA, 18:2n-6) to AA were investigated [12].
• OA, AA or LA did not change, but ALA enhanced tight junction permeability [13].
• Lesser amounts of 9,12-octadecadienoic acid in less-pigmented cell walls may have been caused by the growth of the fungus under environmental stress conditions [14].
• The effect of 13-hydroperoxyoctadecadienoic acid (13-HPODE), a hydroperoxy adduct of linoleic acid (LA), on the activities of prostaglandin (PG) synthesizing and catabolizing enzymes in rabbit gastric antral mucosa was examined [15].
• The content of arachidonic and docosahexaenoic acid, the main products of the conversion of LA and ALA respectively, decreased, LA content increased and a decrease in the unsaturation index was observed in liver microsomes of B6-deficient rats [16].

Associations of Linoleate with other chemical compounds

• Polymorphism of linoleic acid (cis-9, cis-12-octadecadienoic acid) and alpha-linolenic acid (cis-9, cis-12, cis-15-octadecatrienoic acid) [17].
• Effect of 200 microM eicosapentaenoic acid (EPA, C20:5 n-3), arachidonic acid (AA, C20: 4 n-6), alpha-linoleic acid (ALA, C18: 3 n-3), linoleic acid (LA, C18: 2 n-6), or oleic acid (OA, C18: 1 n-9) enrichment in the culture medium during 24 hours were compared [13].
• Butyric acid, alpha-linoleic acid, and docosahexaenoic acid (DHA) were supplemented at 200 microM concentration in the medium of cell cultures [18].
• We compared the effects of oleic acid (OA) and linoleic acid (LA) on variables related with coagulation and fibrinolysis in healthy subjects [19].
• Further, when DHA was administered to cells along with LA + E2, no change in BRCA1 expression was observed, however, a marked decrease in proliferation and soft agar colony formation was evident, indicating inhibition of MCF-7 cells following DHA treatment [20].

Gene context of Linoleate

• This is the first demonstration of glucuronidation of LA and its oxidized derivatives, 13-HODE and 13-OXO, by HLM and recombinant UGT2B7 [21].
• No differences between the OA and LA diets were found in the plasma levels of fibrinogen, plasminogen activator inhibitor, antithrombin III, von Willebrand factor antigen or D-dimers [19].
• Here we measured inhibition of the oxidation of linoleic acid (LA) in authentic fluid from rat small intestine (RIF) by two dietary polyphenols, a flavonoid, epicatechin (EC), and a stilbene, resveratrol (RV), and by gallic (GA) and caffeic (CA) acids, and their partition coefficients [22].
• However, only wild-type p53 transcripts were amplified by RT-PCR of MOLT-4 cells exposed to phytohaemagglutinin, linoleic acid or linolelaidic acid [23].
• The ability of LA to promote cancer progression is accomplished by its intracellular metabolism to 13-hydroxyoctadecadienoic acid (13-HODE) which amplifies the activity of the epidermal growth factor receptor/mitogen-activated protein kinase pathway leading to cell proliferation [24].

Analytical, diagnostic and therapeutic context of Linoleate

• A dietary intervention study with healthy human volunteers that incorporated alpha-LA-rich vegetable oil (flaxseed oil), against a background diet low in LA, allowed us to examine these relationships [25].
• We tested the ability of constant light exposure to suppress MLT production in female nude rats and stimulate the growth of tissue-isolated MCF-7 human breast cancer xenografts via increased tumor linoleic acid (LA) metabolism [26].
• Generally, our data showed a marked immunomodulatory effect of 18-3 (n-3) alpha-linoleic acid on the exhaustive exercise-related immunosuppression, as compared to the effects of other selected PUFA [27].
• It was found that the developed HPLC analysis was able to adequately separate the geometric isomers, linoleic acid (18:2 delta 9c, 12c) from linolelaidic acid (18:2 delta 9t, 12t) [28].

References