Arachidonate 12-Lipoxygenases

Yamamoto, Shozo; Yoshimoto, Tanihiro; Ueda, Natsuo; Hiroshima, Akinori; Takahashi, Yoshitaka; Suzuki, Hiroshi; Natsui, Kiyoshi; Maruyama, Takayuki; Shinjo, Fukiko; Komatsú, Noriyuki; Gerozissis, Kyriaki; Dray, F.; Yokoyama, Chieko; Takai, Toshiyuki; Tanabe, Takayuki

doi:10.1016/b978-0-12-584552-6.50021-5

Cited by 7 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Existing terminology in the literature is confusing; the rodent, leukocyte-type, 12-lipoxygenase is called Alox15 (46,47). Despite the name, the rodent Alox15 is in reality a 12-lipoxygenase that may also have lesser 15-lipoxygenase activity, although in our studies, as described below, we did not detect any 15-lipoxygenase products (i.e., 15-HETE).…”

Section: Discussioncontrasting

confidence: 48%

Induction of arachidonate 12-lipoxygenase (Alox15) in intestine of iron-deficient rats correlates with the production of biologically active lipid mediators

Collins¹,

Hu²,

Ranganathan³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

To identify novel genes associated with iron metabolism, we performed gene chip studies in two models of iron deficiency: iron-deprived rats and rats deficient in the principal intestinal iron transporter, divalent metal transporter 1 (i.e., Belgrade rats). Affymetrix rat genome gene chips were utilized (RAE230) with cRNA samples derived from duodenum and jejunum of experimental and control animals. Computational analysis and statistical data reduction identified 29 candidate genes, which were induced in both models of iron deficiency. Gene ontology analysis showed enrichment for genes related to lipid homeostasis, and one gene related to this physiological process, a leukocyte type, arachidonate 12-lipoxygenase (Alox15), was selected for further examination. TaqMan real-time PCR studies demonstrated strong induction of Alox15 throughout the small and large intestine, and in the liver of iron-deficient rats. Polyclonal antibodies were developed and utilized to demonstrate that proteins levels are significantly increased in the intestinal epithelium of iron-deprived rats. HPLC analysis revealed altered intestinal lipid metabolism indicative of Alox15 activity, which resulted in the production of biologically active lipid molecules (12-HETE, 13-HODE, and 13-HOTE). The overall effect is a perturbation of intestinal lipid homeostasis, which results in the production of lipids essentially absent in the intestine of control rats. We have thus provided mechanistic insight into the alteration in lipid metabolism that occurs during iron deficiency, in that induction of Alox15 mRNA expression may be the primary event. The resulting lipid mediators may be related to documented alterations in villus structure and cell proliferation rates in iron deficiency, or to structural alterations in membrane lipid composition.

show abstract

Section: Discussioncontrasting

confidence: 48%

Induction of arachidonate 12-lipoxygenase (Alox15) in intestine of iron-deficient rats correlates with the production of biologically active lipid mediators

Collins¹,

Hu²,

Ranganathan³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…The other subtype, commonly referred to as leukocyte-type 12-LO, has been found in murine, porcine, bovine, and canine species. Leukocyte 12-LO is very different from platelet 12-LO and more closely related to mammalian 15-LO (577). The biochemical activity of 15-LO is quite distinct and differs from that of the other lipoxygenases in several ways.…”

Section: Lipoxygenases and Lo-dependent Productsmentioning

confidence: 97%

Role of Monocytes in Atherogenesis

Østerud

Bjørklid

2003

Physiological Reviews

358

270

View full text Add to dashboard Cite

This review focuses on the role of monocytes in the early phase of atherogenesis, before foam cell formation. An emerging consensus underscores the importance of the cellular inflammatory system in atherogenesis. Initiation of the process apparently hinges on accumulating low-density lipoproteins (LDL) undergoing oxidation and glycation, providing stimuli for the release of monocyte attracting chemokines and for the upregulation of endothelial adhesive molecules. These conditions favor monocyte transmigration to the intima, where chemically modified, aggregated, or proteoglycan- or antibody-complexed LDL may be endocytotically internalized via scavenger receptors present on the emergent macrophage surface. The differentiating monocytes in concert with T lymphocytes exert a modulating effect on lipoproteins. These events propagate a series of reactions entailing generation of lipid peroxides and expression of chemokines, adhesion molecules, cytokines, and growth factors, thereby sustaining an ongoing inflammatory process leading ultimately to lesion formation. New data emerging from studies using transgenic animals, notably mice, have provided novel insights into many of the cellular interactions and signaling mechanisms involving monocytes/macrophages in the atherogenic processes. A number of these studies, focusing on mechanisms for monocyte activation and the roles of adhesive molecules, chemokines, cytokines and growth factors, are addressed in this review.

show abstract

“…Hydroperoxy fatty acids have multiple functions for LOXs. They convert catalytically silent ferrous LOX species to their active ferric forms (26), but they also inactivate LOX-isoforms irreversibly (27). Moreover, they constitute suitable LOX substrates, which are converted via multiple catalytic activities of the enzymes to secondary reaction products (28,19,30).…”

Section: Maldi-tof Analysis Of the Modified Cleavage Peptidesmentioning

confidence: 99%

Affinity Labeling of the Rabbit 12/15-Lipoxygenase Using Azido Derivatives of Arachidonic Acid

et al. 2006

View full text Add to dashboard Cite

Lipoxygenases are lipid-peroxidizing enzymes, which have been implicated in the pathogenesis of important diseases. They consist of a single polypeptide chain, which is folded into a two-domain structure. The large catalytic domain contains the putative substrate-binding pocket and the catalytic non-heme iron. To identify structural elements of the rabbit 12/15-lipoxygenase that are involved in enzyme/substrate and/or enzyme/product interaction, we synthesized a set of radioactively labeled lipoxygenase substrates carrying a photoreactive azido group (17-azido-ETE, 18-azido-ETE, 19-azido-ETE) and used these compounds as affinity probes. After photoaffinity labeling, the enzyme was digested proteolytically and modified tryptic cleavage peptides were identified by a combination of radio-HPLC and mass spectral analysis. Following this strategy, we observed covalent linkage of a cleavage peptide that contained Ile593, which has previously been identified as the sequence determinant for the positional specificity. These data are consistent with the previous suggestion that this peptide lines the substrate-binding pocket. Surprisingly, we also observed strong labeling of cleavage peptides originating from the N-terminal beta-barrel domain, and our mass spectral data suggested covalent linkage of oxidized affinity probes. Taken together, these results confirm the previous conclusion that Ile593 and surrounding amino acids are constituents of the active site, but they also implicate the N-terminal beta-barrel in enzyme/substrate and/or enzyme/product interaction.

show abstract

Arachidonate 12-Lipoxygenases

Cited by 7 publications

References 30 publications

Induction of arachidonate 12-lipoxygenase (Alox15) in intestine of iron-deficient rats correlates with the production of biologically active lipid mediators

Induction of arachidonate 12-lipoxygenase (Alox15) in intestine of iron-deficient rats correlates with the production of biologically active lipid mediators

Role of Monocytes in Atherogenesis

Affinity Labeling of the Rabbit 12/15-Lipoxygenase Using Azido Derivatives of Arachidonic Acid

Contact Info

Product

Resources

About