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Metabolic and Structural Functions of Lipoxygenases in Skin

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Lipids and Skin Health

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Abstract

Skin is an abundant source of lipoxygenases (LOX). All known LOX genes are expressed in human and mouse skin, respectively. Aberrant expression of individual LOX genes and overshooting enzymatic activities have been found to be associated with acute skin inflammation and chronic inflammatory diseases including atopic dermatitis, psoriasis and others and epithelial cancer. In addition to the pathophysiologic effects, an important structural function in the maintenance of skin permeability barrier could be attributed to two recently described novel LOX, i.e. 12R-LOX and eLOX-3. This is evidenced by genetic studies showing that loss-of-function mutations in the corresponding human LOX genes, ALOX12B and ALOXE3, are linked to the development of autosomal recessive congenital ichthyosis and by gene knockout studies in mice showing that targeted LOX gene inactivation leads to a post-natal lethal phenotype which is due to a severely impaired inwards and outwards permeability barrier function. Data from the LOX knockout mouse models and from in vitro organotypic skin equivalents indicate that LOX action in barrier function can be traced back to the oxidation of the linoleate moiety of ω-hydroxyacyl ceramides which constitutes an important step in the formation of the corneocyte lipid envelope as an indispensable structural component of the epidermal barrier.

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Abbreviations

ARCI:

Autosomal recessive congenital ichthyoses

CE:

Cornified cell envelope

CLE:

Corneocyte lipid envelope

e12-LOX:

Epidermis-type 12-lipoxygenase

EFA:

Essential fatty acid(s)

eLOX-3:

epidermis-type lipoxygenase-3

EOS:

Esterified omega-hydroxyacyl-sphingosine(s)

(F)FA:

(Free) fatty acid(s)

GlcCer:

Glucosylceramide(s)

H(P)ETE:

Hydro(pero)xyeicosatetraenoic acid

H(P)ODE:

Hydro(pero)xyoctadecadienoic acid

HxA, HxB:

Hepoxilin A or B

l12-LOX:

Leukocyte-type 12-lipoxygenase

LOX:

Lipoxygenases(s)

OS:

Omega-hydroxyacyl-sphingosine(s)

p12-LOX:

Platelet-type 12-lipoxygenase

PUFA:

Polyunsaturated fatty acids

TEWL:

Transepidermal water loss

VLC-FA:

Very long chain fatty acid(s)

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Acknowledgments

This work was supported by grants from the Deutsche Forschungsgemeinschaft (KR 905/6-2, KR 905/7-1).

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  1. Genome Modifications and Carcinogenesis, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Sabine Rosenberger, Gerhard Fürstenberger & Peter Krieg

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  1. Sabine Rosenberger
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  2. Gerhard Fürstenberger
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  3. Peter Krieg
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Correspondence to Peter Krieg .

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  1. Johnson & Johnson, Skillman, New Jersey, USA

    Apostolos Pappas

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Rosenberger, S., Fürstenberger, G., Krieg, P. (2015). Metabolic and Structural Functions of Lipoxygenases in Skin. In: Pappas, A. (eds) Lipids and Skin Health. Springer, Cham. https://doi.org/10.1007/978-3-319-09943-9_17

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