The Hepoxilins

Pace-Asciak, Cecil R.; Reynaud, Dénis; Demin, Peter; Nigam, Santosh

doi:10.1007/978-1-4615-4861-4_12

Cited by 50 publications

(50 citation statements)

References 64 publications

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“…Furthermore, we have recently demonstrated that the chemoattractant responsible for S. typhimurium-induced PMN migration across intestinal epithelial monolayers is the eicosanoid HXA 3 and this molecule is produced and/or secreted in a PKC-dependent manner (15). This arachidonic acid metabolite is one of the products of the 12-LO pathway and has been previously shown to stimulate Ca 2ϩ release within PMNs as well as to possess PMN chemotactic activity (13,16). Likewise, we demonstrate in this report that PA infection of A549 cells also results in activation of this novel signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

“…HXA 3 is an arachidonic acid metabolite synthesized mainly through the actions of 12-lipoxygenases, which can induce the release of calcium from intracellular stores of various cell types, including PMNs, via an intracellular G protein-coupled receptor (13). This action has been reported to result in a diverse array of biological functions in various cell types, including; the stimulation of insulin secretion from pancreatic islets of Langerhans, the regulation of cell volume in platelets, and the stimulation of PMN chemotaxis (13)(14)(15)(16). Our studies herein suggest a role for HXA 3 in the directed migration of PMNs across lung epithelial monolayers infected with pathogenic bacteria.…”

Section: Iseases Involving Bacterial-induced Lung Inflammationmentioning

confidence: 99%

“…This molecule, previously termed pathogen-elicited epithelial chemoattractant, was identified as HXA 3 (15). HXA 3 is an eicosanoid metabolized from arachidonic acid (13). The enzyme that is largely responsible for the synthesis of HXA 3 from arachidonic acid is 12-lipoxygenase (12-LO).…”

Section: Bacterial-induced Pmn Transmigration Involves Hxamentioning

confidence: 99%

“…The enzyme that is largely responsible for the synthesis of HXA 3 from arachidonic acid is 12-lipoxygenase (12-LO). 12-LO converts arachadonic acid to 12-hydroxyperoxyeicosatetranoic acid (12-HpETE), which can then be converted to HXA 3 (13). We therefore investigated whether bacterial-induced PMN transmigration across the lung epithelial cells requires 12-LO activity.…”

Section: Bacterial-induced Pmn Transmigration Involves Hxamentioning

confidence: 99%

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Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3

Hurley

Siccardi

Mrsny

et al. 2004

The Journal of Immunology

161

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Lung inflammation resulting from bacterial infection of the respiratory mucosal surface in diseases such as cystic fibrosis and pneumonia contributes significantly to the pathology. A major consequence of the inflammatory response is the recruitment and accumulation of polymorphonuclear cells (PMNs) at the infection site. It is currently unclear what bacterial factors trigger this response and exactly how PMNs are directed across the epithelial barrier to the airway lumen. An in vitro model consisting of human PMNs and alveolar epithelial cells (A549) grown on inverted Transwell filters was used to determine whether bacteria are capable of inducing PMN migration across these epithelial barriers. A variety of lung pathogenic bacteria, including Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa are indeed capable of inducing PMN migration across A549 monolayers. This phenomenon is not mediated by LPS, but requires live bacteria infecting the apical surface. Bacterial interaction with the apical surface of A549 monolayers results in activation of epithelial responses, including the phosphorylation of ERK1/2 and secretion of the PMN chemokine IL-8. However, secretion of IL-8 in response to bacterial infection is neither necessary nor sufficient to mediate PMN transepithelial migration. Instead, PMN transepithelial migration is mediated by the eicosanoid hepoxilin A3, which is a PMN chemoattractant secreted by A549 cells in response to bacterial infection in a protein kinase C-dependent manner. These data suggest that bacterial-induced hepoxilin A3 secretion may represent a previously unrecognized inflammatory mechanism occurring within the lung epithelium during bacterial infections.

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Section: Discussionmentioning

confidence: 99%

Section: Iseases Involving Bacterial-induced Lung Inflammationmentioning

confidence: 99%

Section: Bacterial-induced Pmn Transmigration Involves Hxamentioning

confidence: 99%

Section: Bacterial-induced Pmn Transmigration Involves Hxamentioning

confidence: 99%

See 2 more Smart Citations

Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3

Hurley

Siccardi

Mrsny

et al. 2004

The Journal of Immunology

161

View full text Add to dashboard Cite

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“…Hepoxilins exist as R-or Sisomers and have potent biological activities that are mediated via an intracellular G-coupled protein receptor [58,59]. The 12R-LOX and eLOX3 genes code for two enzymes, 12R-lipoxygenase and a hydroperoxide isomerase (hepoxilin synthase), respectively, that act sequentially on arachidonic acid to synthesize the epoxyalcohol product (8R-hydroxy-11,12-epoxyeicosa-5Z,9E,14Z-trienoic acid) referred to as (R)-hepoxilin-A3 [abbreviated (R)-HXA3] [60].…”

Section: Cutaneous Pathogenesismentioning

confidence: 99%

Sjögren–Larsson syndrome: Molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency

Rizzo

2007

Molecular Genetics and Metabolism

140

159

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Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase (FALDH), an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. Affected patients display ichthyosis, mental retardation and spastic diplegia. More than 70 mutations in ALDH3A2 have been discovered in SLS patients including amino acid substitutions, deletions, insertions and splicing errors. Most mutations are private, but several common mutations reflect founder effects, consanguinity or recurrent mutational events. FALDH oxidizes fatty aldehyde substrates arising from metabolism of fatty alcohols, leukotriene B4, ether glycerolipids and other potential sources such as sphingolipids. The pathogenesis of the cutaneous and neurologic symptoms is thought to result from abnormal lipid accumulation in the membranes of skin and brain; the formation of aldehyde Schiff base adducts with amine-containing lipids or proteins; or defective eicosanoid metabolism. Therapeutic approaches are being developed to target specific metabolic defects associated with FALDH deficiency or to correct the genetic defect by gene transfer.

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LOX‐Induced Lipid Peroxidation Mechanism Responsible for the Detrimental Effect of Marine Diatoms on Zooplankton Grazers

et al. 2007

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Some marine diatoms negatively affect the reproduction of dominant zooplankton grazers such as copepods, thus compromising the transfer of energy through the marine food chains. In this paper, the metabolic mechanism that leads to diatom-induced toxicity is investigated in three bloom-forming microalgae. We show that copepod dysfunctions can be induced by highly reactive oxygen species (hROS) and a blended mixture of diatom products, including fatty acid hydroperoxides (FAHs); these compounds display teratogenic and proapoptotic properties. The process is triggered by the early onset of lipoxygenase activities that elicit the synthesis of species-specific products, the basic structures of which were established (1-20); these compounds boost oxidative stress by massive lipid peroxidation. Our study might explain past laboratory and field results showing how diatoms damage zooplankton grazers even in the absence of polyunsaturated aldehydes, a class of molecules that has been formerly implicated in mediating the toxic activity of diatoms on copepods.

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The Hepoxilins

Cited by 50 publications

References 64 publications

Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3

Polymorphonuclear Cell Transmigration Induced by Pseudomonas aeruginosa Requires the Eicosanoid Hepoxilin A3

Sjögren–Larsson syndrome: Molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency

LOX‐Induced Lipid Peroxidation Mechanism Responsible for the Detrimental Effect of Marine Diatoms on Zooplankton Grazers

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