Enzymes and receptors in the leukotriene cascade

Haeggström, Jesper Z.; Wetterholm, Anders

doi:10.1007/s00018-002-8463-1

Cited by 79 publications

(37 citation statements)

References 134 publications

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“…Arachidonic acid liberated by PLA 2 s is converted to eicosanoids (9,28). Lysophospholipids are also precursors for a different class of lipid mediators including PAF, LPA, and endocannabinoids (29)(30)(31)(32)(33)(34)(35) (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

Hishikawa

Shindou²,

Kobayashi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

284

282

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All organisms consist of cells that are enclosed by a cell membrane containing bipolar lipids and proteins. Glycerophospholipids are important not only as structural and functional components of cellular membrane but also as precursors of various lipid mediators. Polyunsaturated fatty acids comprising arachidonic acid or eicosapentaenoic acid are located at sn-2 position, but not at sn-1 position of glycerophospholipids in an asymmetrical manner. In addition to the asymmetry, the membrane diversity is important for membrane fluidity and curvature. To explain the asymmetrical distribution of fatty acids, the rapid turnover of sn-2 position was proposed in 1958 by Lands [Lands WE (1958) Metabolism of glycerolipides: A comparison of lecithin and triglyceride synthesis. J Biol Chem 231:883-888]. However, the molecular mechanisms and biological significance of the asymmetry remained unknown. Here, we describe a putative enzyme superfamily consisting mainly of three gene families, which catalyzes the transfer of acyl-CoAs to lysophospholipids to produce different classes of phospholipids. Among them, we characterized three important enzymes with different substrate specificities and tissue distributions; one, termed lysophosphatidylcholine acyltransferase-3 (a mammalian homologue of Drosophila nessy critical for embryogenesis), prefers arachidonoyl-CoA, and the other two enzymes incorporate oleoyl-CoAs to lysophosphatidylethanolamine and lysophosphatidylserine. Thus, we propose that the membrane diversity is produced by the concerted and overlapped reactions with multiple enzymes that recognize both the polar head group of glycerophospholipids and various acyl-CoAs. Our findings constitute a critical milestone for our understanding about how membrane diversity and asymmetry are established and their biological significance.glycerophospholipids ͉ Lands' cycle ͉ membrane remodeling ͉ phospholipase A 2 ͉ acyl-CoA

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Section: Discussionmentioning

confidence: 99%

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

Hishikawa

Shindou²,

Kobayashi³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

284

282

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“…Common to these GPCR systems is activation of PLC through G␣q (13)(14)(15)(16)(17)(18). To determine whether G␣q plays a key role in progression of glomerular diseases, we expressed a constitutively active G␣q in glomerular podocytes using the mouse nephrin promoter (29,30).…”

Section: Discussionmentioning

confidence: 99%

“…These injury-promoting GPCR systems are found in podocytes (2) and, thus, may contribute to podocyte injury in disease states. Although the signaling pathways that are activated by these GPCR are diverse (13)(14)(15)(16)(17)(18), common to all of these receptor systems is activation of phospholipase C (PLC) through G␣q (13)(14)(15)(16)(17)(18). Activation of PLC generates the second messengers diacyl glycerol (DAG) and inositol phosphates (IP).…”

mentioning

confidence: 99%

Activation of Gαq-Coupled Signaling Pathways in Glomerular Podocytes Promotes Renal Injury

Wang

Fields²,

Pazmino³

et al. 2005

Journal of the American Society of Nephrology

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The glomerular podocyte plays a key role in maintaining the integrity of the glomerular filtration barrier. This function may be regulated by activation of cell surface G protein-coupled receptors (GPCR). Studies suggest that podocytes express GPCR that are implicated in the pathogenesis of glomerular diseases. Common to these GPCR systems is activation of phospholipase C through the Gq ␣-subunit (G␣q). For investigating the role of G␣q-coupled signaling pathways in promoting renal injury in podocytes, a constitutively active G␣q subunit (G␣qQ>L) was expressed in glomerular podocytes using the mouse nephrin promoter. Transgenic (TG) mice demonstrated albuminuria as well as a decrease in both kidney mass and nephron number. By light microscopy, a portion of the TG mice had glomerular abnormalities, including focal to diffuse hypercellularity and segmental sclerosis. Consistent with injury-promoting effects of G␣qQ>L, there was a significant reduction in podocalyxin mRNA as well as nephrin mRNA and protein levels in glomeruli from TG mice compared with non-TG controls. Expression of the transgene also seemed to increase susceptibility to glomerular injury, because treatment with puromycin aminonucleoside enhanced proteinuria in TG mice compared with non-TG littermate controls (4.2 ؎ 1.0 [TG] versus 1.6 ؎ 0.3 [non-TG] mg/24 h; P ‫؍‬ 0.0161). Thus, activation of G␣q in glomerular podocytes caused alterations in glomerular histomorphology, albuminuria, decreased nephron mass, and reduced glomerular expression of both nephrin and podocalyxin as well as enhanced susceptibility to glomerular damage induced by puromycin aminonucleoside. It is speculated that G␣q-coupled signaling cascades may be important effector pathways mediating renal injury.

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“…These compounds are not stable and, through hydroxyderivates, they form stable compounds with carbonyl groups. Some of these compounds are used as markers of oxidative stress 26 . Linoleic acid, EPA, Mead acid (20:3n-9) and DHA may be substrates for lipoperoxidation.…”

Section: Fatty Acids and Lipoperoxidationmentioning

confidence: 99%

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

Kremmyda¹,

Tvrzická²,

Staňková³

et al. 2011

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

153

134

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Background. This is the second of two review parts aiming at describing the major physiological roles of fatty acids, as well as their applications in specific conditions related to human health.Results. The review included the current literature published in Pubmed up to March 2011. In humans, fatty acids are a principle energy substrate and structural components of cell membranes (phospholipids) and second messengers. Fatty acids are also ligands of nuclear receptors affecting gene expression. Longer-chain (LC) polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid are precursors of lipid mediators such as eicosanoids (prostaglandins, leukotrienes, thromboxanes), resolvins and neuroprotectins. Lipid mediators produced by EPA and DHA (LC n-3 PUFA; mainly found in oily fish) are considered as inflammation-resolving, and thus, fish oil has been characterised as antiinflammatory. Recommendations for EPA plus DHA intake from oily fish vary between 250-450 mg/day. Dietary reference values for fat vary between nutrition bodies, but mainly agree on a low total and saturated fat intake. The existing literature supports the protective effects of LC n-3 PUFA (as opposed to n-6 PUFA and saturated fat) in maternal and offspring health, cardiovascular health, insulin sensitivity, the metabolic syndrome, cancer, critically ill patients, and immune system disorders.Conclusion. Fatty acids are involved in multiple pathways and play a major role in health. Further investigation and a nutrigenomics approach to the effects of these biocompounds on health and disease development are imperative and highlight the importance of environmental modifications on disease outcome.humans. Thus, these FA may be characterised as conditionally essential depending on EFA availability. Genetic variation in human desaturase genes affects FA metabolism, plasma lipid profiles, and risk of disease development [5][6][7] . Recommendations for minimum dietary intake of EPA plus DHA vary between 250-450 mg/day 8 , especially for pregnant women and those of reproductive age. Rich sources of LC n-3 PUFA are fish oils and the flesh of oily fish, whereas non-oily (white) fish contain them but in lower amounts.Long-chain PUFA with 18-20 carbon atoms, including EPA and AA, are precursors of eicosanoids (prostaglandins, leucotrienes and thromboxanes), which have a broad scale of regulatory, autocrine and paracrine effects. Long-chain PUFA with 20 and 22 carbon atoms are precursors of autacoids -resolvins (resolution phase interaction products), lipoxins and neuroprotectins 9 . FA are also ligands of nuclear receptors which take part in the subcellular control of metabolic pathways. Covalent modification of proteins by FA acylation enables their incorporation into membranes. Hydroxy FA are activators of some nuclear factors and are responsible for the expression of proinflammatory cytokines (interleukin (IL)-1,

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Enzymes and receptors in the leukotriene cascade

Cited by 79 publications

References 134 publications

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

Discovery of a lysophospholipid acyltransferase family essential for membrane asymmetry and diversity

Activation of Gαq-Coupled Signaling Pathways in Glomerular Podocytes Promotes Renal Injury

Fatty Acids as Biocompounds: Their Role in Human Metabolism, Health and Disease - A Review. Part 2: Fatty Acid Physiological Roles and Applications in Human Health and Disease

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