Epidermis-type lipoxygenases

Krieg, Peter; Heidt, Markus; Siebert, Malte; Kinzig, Andreas; Marks, Friedrich; Fürstenberger, Gerhard

doi:10.1016/s0090-6980(99)90431-8

Cited by 7 publications

(8 citation statements)

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“…In humans, 12R-LOX has been detected in keratinocytes, tonsil squamous epithelial cells, bronchial epithelial cells, and psoriasis scales, as well as in B cells [8,70–74] . In mice, its expression has been induced at embryonic day (E) 15.5 in the epidermis, nasal epithelium, and surface of the tongue, suggesting that 12R-LOX is required for the proper development of neonates [71] .…”

Section: -Lipoxygenase 12r Type (12r-lox)mentioning

confidence: 99%

The role of lipoxygenases in pathophysiology; new insights and future perspectives

2015

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Lipoxygenases (LOXs) are dioxygenases that catalyze the formation of corresponding hydroperoxides from polyunsaturated fatty acids such as linoleic acid and arachidonic acid. LOX enzymes are expressed in immune, epithelial, and tumor cells that display a variety of physiological functions, including inflammation, skin disorder, and tumorigenesis. In the humans and mice, six LOX isoforms have been known. 15-LOX, a prototypical enzyme originally found in reticulocytes shares the similarity of amino acid sequence as well as the biochemical property to plant LOX enzymes. 15-LOX-2, which is expressed in epithelial cells and leukocytes, has different substrate specificity in the humans and mice, therefore, the role of them in mammals has not been established. 12-LOX is an isoform expressed in epithelial cells and myeloid cells including platelets. Many mutations in this isoform are found in epithelial cancers, suggesting a potential link between 12-LOX and tumorigenesis. 12R-LOX can be found in the epithelial cells of the skin. Defects in this gene result in ichthyosis, a cutaneous disorder characterized by pathophysiologically dried skin due to abnormal loss of water from its epithelial cell layer. Similarly, eLOX-3, which is also expressed in the skin epithelial cells acting downstream 12R-LOX, is another causative factor for ichthyosis. 5-LOX is a distinct isoform playing an important role in asthma and inflammation. This isoform causes the constriction of bronchioles in response to cysteinyl leukotrienes such as LTC4, thus leading to asthma. It also induces neutrophilic inflammation by its recruitment in response to LTB4. Importantly, 5-LOX activity is strictly regulated by 5-LOX activating protein (FLAP) though the distribution of 5-LOX in the nucleus. Currently, pharmacological drugs targeting FLAP are actively developing. This review summarized these functions of LOX enzymes under pathophysiological conditions in mammals.

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Section: -Lipoxygenase 12r Type (12r-lox)mentioning

confidence: 99%

The role of lipoxygenases in pathophysiology; new insights and future perspectives

2015

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“…ALOX12B and ALOXE3 encode the lipoxygenases 12R-LOX and epidermal LOX-3 (eLOX-3), respectively. Both are members of the epidermal subfamily of mammalian LOX with preferential expression in the skin and several other epithelial tissues (Krieg et al, 2002). LOXs constitute a widespread family of non-heme iron dioxygenases that insert molecular oxygen into polyunsaturated fatty acids, producing highly active lipid mediators (Brash, 1999).…”

Section: Introductionmentioning

confidence: 99%

Aloxe3 Knockout Mice Reveal a Function of Epidermal Lipoxygenase-3 as Hepoxilin Synthase and Its Pivotal Role in Barrier Formation

Krieg

Rosenberger

Juanes

et al. 2013

Journal of Investigative Dermatology

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116

124

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Loss-of-function mutations in the lipoxygenase (LOX) genes ALOX12B and ALOXE3 are the second most common cause of autosomal recessive congenital ichthyosis. The encoded proteins, 12R-LOX and epidermal LOX-3 (eLOX-3), act in sequence to convert fatty acid substrates via R-hydroperoxides to specific epoxyalcohol derivatives and have been proposed to operate in the same metabolic pathway during epidermal barrier formation. Here, we show that eLOX-3 deficiency in mice results in early postnatal death, associated with similar but somewhat less severe barrier defects and morphological changes than reported earlier for the 12R-LOX-knockout mice. Skin lipid analysis demonstrated that the severity of barrier failure is related to the loss of covalently bound ceramides in both 12R-LOX- and eLOX-3-null mice, confirming a proposed functional linkage of the LOX pathway to ceramide processing and formation of the corneocyte lipid envelope. Furthermore, analysis of free oxygenated fatty acid metabolites revealed strongly reduced levels of hepoxilin metabolites in eLOX-3-deficient epidermis, indicating an additional function of eLOX-3 in mammalian skin as a hepoxilin synthase linked to the 12S-LOX pathway.

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“…Lipoxygenases (LOXs) represent a widely distributed family of nonheme, nonsulfur, iron-containing dioxygenases that catalyze the regioselective and stereoselective dioxygenation of fatty acid substrates containing one or more (Z,Z)-1,4pentadiene moieties (Brash, 1999). Within the mammalian LOX family, a distinct subclass of epidermis-type LOX has been characterized that are preferentially expressed in skin and few other epithelial tissues (Krieg et al, 2002). They include the human 15-LOX-2 and its mouse orthologue 8-LOX, 12R-LOX, and eLOX-3.…”

Section: Introductionmentioning

confidence: 99%

12R-lipoxygenase deficiency disrupts epidermal barrier function

Epp

Fürstenberger

Müller

et al. 2007

The Journal of Cell Biology

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173

172

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12R-lipoxygenase (12R-LOX) and the epidermal LOX-3 (eLOX-3) constitute a novel LOX pathway involved in terminal differentiation in skin. This view is supported by recent studies showing that inactivating mutations in 12R-LOX and eLOX-3 are linked to the development of autosomal recessive congenital ichthyosis. We show that 12R-LOX deficiency in mice results in a severe impairment of skin barrier function. Loss of barrier function occurs without alterations in proliferation and stratified organization of the keratinocytes, but is associated with ultrastructural anomalies in the upper granular layer, suggesting perturbance of the assembly/extrusion of lamellar bodies. Cornified envelopes from skin of 12R-LOX–deficient mice show increased fragility. Lipid analysis demonstrates a disordered composition of ceramides, in particular a decrease of ester-bound ceramide species. Moreover, processing of profilaggrin to monomeric filaggrin is impaired.This study indicates that the 12R-LOX–eLOX-3 pathway plays a key role in the process of epidermal barrier acquisition by affecting lipid metabolism, as well as protein processing.

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Epidermis-type lipoxygenases

Cited by 7 publications

References 0 publications

The role of lipoxygenases in pathophysiology; new insights and future perspectives

The role of lipoxygenases in pathophysiology; new insights and future perspectives

Aloxe3 Knockout Mice Reveal a Function of Epidermal Lipoxygenase-3 as Hepoxilin Synthase and Its Pivotal Role in Barrier Formation

12R-lipoxygenase deficiency disrupts epidermal barrier function

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