Acyl-chain selectivity of the 85 kDa phospholipase A2 and of the release process in intact macrophages

Sundler, Roger; Winstedt, Dag; Wijkander, Jonny

doi:10.1042/bj3010455

Cited by 24 publications

(13 citation statements)

References 27 publications

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“…A careful comparison revealed that the area showing decrease of individual PCs and that showing increase of individual LPCs only roughly overlapped with each other. Difference in substrate affinity of ischemiaupregulated brain PLA 2 [44][45][46] was likely a contributing factor to such disparity. Conversely, the distribution of LPCs represented the cumulative effects of upregulated PLA 2 toward the parenchymal PCs that was not likely represented by the change of individual PCs.…”

Section: Discussionmentioning

confidence: 99%

MALDI-mass spectrometry imaging of desalted rat brain sections reveals ischemia-mediated changes of lipids

Wang

Tsai

et al. 2012

Anal Bioanal Chem

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Ischemia-mediated lipidomic changes in rat brains were explored by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) profiling and imaging after in situ desalting which drastically simplified the spectral presentation of tissue lipids. Removal of interference from the massively changed cations in response to tissue damage permitted the revelation of subtle yet important lipidomic changes. The identities of the detected lipids were confirmed by MALDI tandem mass spectrometry (MALDI-MS/MS). The MALDI-MS imaging (MALDI-MSI) result of lysophosphatidylcholine 16:0 (LPC 16:0) in the desalted brain section appeared essentially identical to that of sodiated LPC 16:0 in the adjacent undesalted section and verified the suitability of the desalting method for the MALDI-MSI studies of lipids in tissue. Other than the consistently decreased phosphatidylcholine (PC) 16:0/18:1, images of PCs containing all saturated, or combined saturated and monounsaturated fatty acyl (MUFA) residues revealed their parenchymal increase by ischemia. Images of PCs containing polyunsaturated fatty acyl (PUFA) residues in normal cortex showed laminated patterns similar to cortical lamina. Ischemia reduced the abundance of PC 16:0/20:4 and PC 16:0/22:6 and disrupted the laminated distribution of the former. However, ischemia increased the subcortical abundance of PUFA-PCs containing stearoyl residue and confined their cortical increase within limited areas. Image of parenchymal sphingomyelin 18:0 (SM 18:0) showed its consistent decrease by ischemia that paralleled the increase of ceramide 18:0-H(2)O in region of moderate to high SM abundance. The above results presented the lipidomic changes largely different from previous MALDI-MSI results and suggested a window of intervention that may benefit the management of cerebrovascular accident and other brain injuries.

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Section: Discussionmentioning

confidence: 99%

MALDI-mass spectrometry imaging of desalted rat brain sections reveals ischemia-mediated changes of lipids

Wang

Tsai

et al. 2012

Anal Bioanal Chem

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“…The 14-kDa PLA 2 s (type I and II) are secretory enzymes, and although they show no apparent preference for hydrolysis of AA-containing phospholipids (4,5), they have been suggested to participate in the generation of eicosanoids after first being secreted by mobilizing AA from phospholipids on the outer leaflet of the plasma membrane (6 -12). The 85-kDa PLA 2 (13,14) is an intracellular enzyme with clear preference for AA-containing phospholipids (5,15,16). Furthermore, the 85-kDa PLA 2 translocates to membranes in response to submicromolar concentrations of Ca 2ϩ (13,17,18) and is also regulated by phosphorylation, which results in an increase in its catalytic activity (19 -21).…”

mentioning

confidence: 99%

5-Lipoxygenase Products Modulate the Activity of the 85-kDa Phospholipase A2 in Human Neutrophils

Wijkander

O’Flaherty

Nixon

et al. 1995

Journal of Biological Chemistry

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14C]arachidonoylphosphatidylcholine as substrate. A similar increase in cytosolic PLA 2 activity was induced by stimulation of neutrophils with leukotriene B 4 (LTB 4 ), 5-oxoeicosatetraenoic acid, or 5-hydroxyeicosatetraenoic acid (5-HETE). LTB 4 was the most potent of the agonists, showing maximal effect at 1 nM. Inhibition of 5-lipoxygenase with either eicosatetraynoic acid or zileuton prevented the AA-induced increase in PLA 2 activity but had no effect on the response induced by LTB 4 . Furthermore, pretreatment of neutrophils with a LTB 4 -receptor antagonist, LY 255283, blocked the AAand LTB 4 -induced activation of PLA 2 but did not influence the action of 5-HETE. Treatment of neutrophils with pancreatic PLA 2 also induced an increase in the activity of the cytosolic PLA 2 ; this response was inhibited by both eicosatetraynoic acid or LY 255283.The increases in PLA 2 activity in response to stimulation correlated with a shift in electrophoretic mobility of the 85-kDa PLA 2 , as determined by Western blot analysis, suggesting that phosphorylation of the 85-kDa PLA 2 likely underlies its increase in catalytic activity. Although stimulation of neutrophils with individual lipoxygenase metabolites did not induce significant mobilization of endogenous AA, they greatly enhanced the N-formylmethionyl-leucyl-phenylalanine-induced mobilization of AA as determined by mass spectrometry analysis. Our findings support a positive-feedback model in which stimulus-induced release of AA or exocytosis of secretory PLA 2 modulate the activity of the cytosolic 85-kDa PLA 2 by initiating the formation of LTB 4 . The nascent LTB 4 is then released to act on the LTB 4 receptor and thereby promote further activation of the 85-kDa PLA 2 . Since 5-HETE and LTB 4 are known to prime the synthesis of platelet-activating factor, the findings suggest that 85-kDa PLA 2 plays a role in platelet-activating factor synthesis.Arachidonic acid (AA) 1 is the precursor for prostaglandins and leukotrienes (collectively named eicosanoids), which together with platelet-activating factor (PAF) are important lipid mediators involved in allergic and inflammatory reactions. The initial step in the production of eicosanoids is hydrolysis of sn-2-arachidonate from membrane phospholipids generating free AA; phospholipase A 2 s (PLA 2 ) with different characteristics have been implicated in this hydrolysis (1-3). The 14-kDa PLA 2 s (type I and II) are secretory enzymes, and although they show no apparent preference for hydrolysis of AA-containing phospholipids (4, 5), they have been suggested to participate in the generation of eicosanoids after first being secreted by mobilizing AA from phospholipids on the outer leaflet of the plasma membrane (6 -12). The 85-kDa PLA 2 (13, 14) is an intracellular enzyme with clear preference for AA-containing phospholipids (5, 15, 16). Furthermore, the 85-kDa PLA 2 translocates to membranes in response to submicromolar concentrations of Ca 2ϩ (13,17,18) and is also regulated by phosphorylation, which results in an inc...

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“…n-3 FA are only a minor fraction of total PUFA and therefore less liable to be replaced. But in contrast to n-6 FA they, especially DHA that is normally the most abundant of the n-3 FA in plasma, do not appear to be effectively released from glycerolipids by phospholipases [29] (Fig. 3).…”

Section: Fat Intakes and Fa Transportmentioning

confidence: 99%

Origin of fatty acids in the body: endogenous synthesis versus dietary intakes

Galli

Risé

2006

Eur. J. Lipid Sci. Technol.

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Origin of fatty acids in the body: endogenous synthesis versus dietary intakesFats, as fatty acids (FA), together with carbohydrates, represent a major substrate group for energy production. In contrast to carbohydrates FA are less efficiently used for energy and more easily stored in tissues. A major issue, still not completely solved, concerns the origin of FA in the organism. The two theoretical alternatives are a) endogenous de novo lipogenesis from carbohydrates, and b) supply through the diet. Various pieces of evidence indicate that the first option, while well-documented in simple biological systems, plays a minimal role in vivo. The exogenous origin therefore represents the preferred, major route of FA supply to the body. This is also supported by the observation that only the enzymes involved in the production of long-chain polyunsaturated FA from their precursors, and not those involved in the synthesis of the FA that are abundant in the diet, are operating in vivo. Finally, as a consequence of the load of fats in our diets, competition for esterification, and reciprocal replacements, of the unsaturated FA and FA classes, that are most abundantly provided by the diet, take place in plasma lipids.

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Acyl-chain selectivity of the 85 kDa phospholipase A2 and of the release process in intact macrophages

Cited by 24 publications

References 27 publications

MALDI-mass spectrometry imaging of desalted rat brain sections reveals ischemia-mediated changes of lipids

MALDI-mass spectrometry imaging of desalted rat brain sections reveals ischemia-mediated changes of lipids

5-Lipoxygenase Products Modulate the Activity of the 85-kDa Phospholipase A2 in Human Neutrophils

Origin of fatty acids in the body: endogenous synthesis versus dietary intakes

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