Quantitative stereochemical analysis of subnanogram amounts of 12-hydroxy-(5,8,10,14)-eicosatetraenoic acid by sequential chiral phase liquid chromatography and stable isotope dilution mass spectrometry

Turk, John; Stump, W. Thomas; Wolf, Bryan A.; Easom, Richard A.; McDaniel, Michael L.

doi:10.1016/0003-2697(88)90059-0

Cited by 12 publications

(6 citation statements)

References 29 publications

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“…6), but this material did not increase in abundance after adding IL-1 to islets (time 2,4,8,24, and 48 h lanes of upper panel of Fig. 6).…”

mentioning

confidence: 89%

“…The stereochemical composition of 12-HETE generated from IL-1-treated islets was therefore determined. Islet 12-lipoxygenase produces exclusively 12-S-HETE, but nonenzymatic lipid peroxidation produces a racemic mixture of 12-S-and 12-R-HETE (8). Stereochemical analyses were performed by addition of racemic […”

Section: '' Displayed Values For Each Parameter Represent the Fold-inmentioning

confidence: 99%

“…Isolated pancreatic islets from rats and humans convert endogenous arachidonic acid to oxygenated metabolites, and islet eicosanoid synthesis is stimulated by insulin secretagogues (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). The most abundant islet eicosanoids are the cyclooxygenase product PGE 2 1 and the 12-lipoxygenase product 12-hydroxy- (5,8,10,14)-eicosatetraenoic acid .…”

mentioning

confidence: 99%

“…The most abundant islet eicosanoids are the cyclooxygenase product PGE 2 1 and the 12-lipoxygenase product 12-hydroxy- (5,8,10,14)-eicosatetraenoic acid . PGE 2 may negatively modulate insulin secretion (11) and exerts proinflammatory effects (12).…”

mentioning

confidence: 99%

“…Fuel insulin secretagogues stimulate islet 12-HETE production; exogenous 12-HPETE, the precursor of 12-HETE, stimulates insulin secretion (1); and pharmacologic inhibitors of 12-lipoxygenase suppress both 12-HETE production and insulin secretion with identical concentration dependences (1)(2)(3)(4)(5)(6)(7)(8). Islet 12-HETE consists exclusively of the S-enantiomer, indicating enzymatic synthesis (9), and immunochemical analyses indicate that islet 12-lipoxygenase is selectively expressed in ␤-cells but not in ␣-cells or in pancreatic exocrine cells (18).…”

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confidence: 99%

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Interleukin-1 Enhances Pancreatic Islet Arachidonic Acid 12-Lipoxygenase Product Generation by Increasing Substrate Availability through a Nitric Oxide-dependent Mechanism

Ramanadham

Corbett

et al. 1996

Journal of Biological Chemistry

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Interleukin-1 (IL-1) impairs insulin secretion from pancreatic islets and may contribute to the pathogenesis of insulin-dependent diabetes mellitus. IL-1 increases islet expression of nitric oxide (NO) synthase, and the resultant overproduction of NO participates in inhibition of insulin secretion because NO synthase inhibitors, e.g. N G -monomethyl-arginine (NMMA), prevent this inhibition. While exploring effects of IL-1 on islet arachidonic acid metabolism, we found that IL-1 increases islet production of the 12-lipoxygenase product 12-hydroxyeicosatetraenoic acid 12-(HETE). This effect requires NO production and is prevented by NMMA. Exploration of the mechanism of this effect indicates that it involves increased availabilty of the substrate arachidonic acid rather than enhanced expression of 12-lipoxygenase. Evidence supporting this conclusion includes the facts that IL-1 does not increase islet 12-lipoxygenase protein or mRNA levels and does not enhance islet conversion of exogenous arachidonate to 12-HETE. Mass spectrometric stereochemical analyses nonetheless indicate that 12-HETE produced by IL-1-treated islets consists only of the S-enantiomer and thus arises from enzyme action. IL-1 does enhance release of nonesterified arachidonate from islets, as measured by isotope dilution mass spectrometry, and this effect is suppressed by NMMA and mimicked by the NO-releasing compound 3-morpholinosydnonimine. Although IL-1 increases neither islet phospholipase A 2 (PLA 2 ) activities nor mRNA levels for cytosolic or secretory PLA 2 , a suicide substrate which inhibits an islet Ca 2؉ -independent PLA 2 prevents enhancement of islet arachidonate release by IL-1. IL-1 also impairs esterification of [ 3 H 8 ]arachidonate into islet phospholipids, and this effect is prevented by NMMA and mimicked by the mitochondrial ATP-synthase inhibitor oligomycin. Experiments with exogenous substrates indicate that NMMA does not inhibit and that the NO-releasing compound does not activate islet 12-lipoxygenase or PLA 2 activities. These results indicate that a novel action of NO is to increase levels of nonesterified arachidonic acid in islets.

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“…6), but this material did not increase in abundance after adding IL-1 to islets (time 2,4,8,24, and 48 h lanes of upper panel of Fig. 6).…”

mentioning

confidence: 89%

Section: '' Displayed Values For Each Parameter Represent the Fold-inmentioning

confidence: 99%