Epidermis-Type Lipoxygenases

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

doi:10.1007/978-1-4615-0193-0_26

Cited by 15 publications

(7 citation statements)

References 12 publications

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“…The most studied LOX enzymes are 5-LOX, leukocyte and platelettype 12-LOX and reticulocyte-type 15-LOX-1; however the mammalian family of LOX isozymes has recently grown to include isozymes preferentially expressed in both human and murine epidermis. These isozymes include epidermal 12-LOX and 12R-LOX (producing products with R chirality), mouse 8-LOX and its human ortholog 15-LOX-2, and epidermal LOX-3 exhibiting hydroperoxide isomerase activity [7,8]. The LOX enzymes metabolize arachidonic acid (AA) to the biologically active metabolites hydroperoxyeicosatetraenoic acids (HPETEs), which upon reduction result in the formation of corresponding HETEs (Fig.…”

Section: Lipoxygenase-catalyzed Arachidonic Acid Metabolismmentioning

confidence: 99%

Lipoxygenase metabolism: roles in tumor progression and survival

Pidgeon

Lysaght

Krishnamoorthy

et al. 2007

Cancer Metastasis Rev

259

206

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The metabolism of arachidonic acid through lipoxygenase pathways leads to the generation of various biologically active eicosanoids. The expression of these enzymes vary throughout the progression of various cancers, and thereby they have been shown to regulate aspects of tumor development. Substantial evidence supports a functional role for lipoxygenase-catalyzed arachidonic and linoleic acid metabolism in cancer development. Pharmacologic and natural inhibitors of lipoxygenases have been shown to suppress carcinogenesis and tumor growth in a number of experimental models. Signaling of hydro[peroxy]fatty acids following arachidonic or linoleic acid metabolism potentially effect diverse biological phenomenon regulating processes such as cell growth, cell survival, angiogenesis, cell invasion, metastatic potential and immunomodulation. However, the effects of distinct LOX isoforms differ considerably with respect to their effects on both the individual mechanisms described and the tumor being examined. 5-LOX and platelet type 12-LOX are generally considered pro-carcinogenic, with the role of 15-LOX-1 remaining controversial, while 15-LOX-2 suppresses carcinogenesis. In this review, we focus on the molecular mechanisms regulated by LOX metabolism in some of the major cancers. We discuss the effects of LOXs on tumor cell proliferation, their roles in cell cycle control and cell death induction, effects on angiogenesis, migration and the immune response, as well as the signal transduction pathways involved in these processes. Understanding the molecular mechanisms underlying the anti-tumor effect of specific, or general, LOX inhibitors may lead to the design of biologically and pharmacologically targeted therapeutic strategies inhibiting LOX isoforms and/or their biologically active metabolites, that may ultimately prove useful in the treatment of cancer, either alone or in combination with conventional therapies.

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Section: Lipoxygenase-catalyzed Arachidonic Acid Metabolismmentioning

confidence: 99%

Lipoxygenase metabolism: roles in tumor progression and survival

Pidgeon

Lysaght

Krishnamoorthy

et al. 2007

Cancer Metastasis Rev

259

206

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“…Journal of Cell Science 122 (9) 12R-LOX is an epidermis-specific member of the LOX multigene family, members of which catalyse the dioxygenation of fatty-acid substrates (Krieg et al, 2002). 12R-LOX-deficient mice have a severely impaired skin barrier and altered lipid composition in the stratum corneum, which results in early postnatal death as a result of transepidermal water loss (Epp et al, 2007).…”

Section: Proteases Implicated In Profilaggrin Processing -Evidence Frmentioning

confidence: 99%

Filaggrin in the frontline: role in skin barrier function and disease

Sandilands

Sutherland

Irvine

et al. 2009

Journal of Cell Science

689

685

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Recently, loss-of-function mutations in FLG, the human gene encoding profilaggrin and filaggrin, have been identified as the cause of the common skin condition ichthyosis vulgaris (which is characterised by dry, scaly skin). These mutations, which are carried by up to 10% of people, also represent a strong genetic predisposing factor for atopic eczema, asthma and allergies. Profilaggrin is the major component of the keratohyalin granules within epidermal granular cells. During epidermal terminal differentiation, the ~400 kDa profilaggrin polyprotein is dephosphorylated and rapidly cleaved by serine proteases to form monomeric filaggrin (37 kDa), which binds to and condenses the keratin cytoskeleton and thereby contributes to the cell compaction process that is required for squame biogenesis. Within the squames, filaggrin is citrullinated, which promotes its unfolding and further degradation into hygroscopic amino acids, which constitute one element of natural moisturising factor. Loss of profilaggrin or filaggrin leads to a poorly formed stratum corneum (ichthyosis), which is also prone to water loss (xerosis). Recent human genetic studies strongly suggest that perturbation of skin barrier function as a result of reduction or complete loss of filaggrin expression leads to enhanced percutaneous transfer of allergens. Filaggrin is therefore in the frontline of defence, and protects the body from the entry of foreign environmental substances that can otherwise trigger aberrant immune responses.

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“…15-LOX-1 is expressed in reticulocytes and eosinophils (Kuhn et al, 1999;Wittwer et al, 2007), and 15-LOX-2 is expressed in the skin, prostate gland, lungs and cornea (Brash et al, 1997;Krieg et al, 2002). Linoleic acid (LA) is the preferred substrate for 15-LOX-1.…”

Section: The Production Of Aa Metabolites By Cox/lox and The Stimulatmentioning

confidence: 99%

Bioactive Lipoxygenase Metabolites Stimulation of NADPH Oxidases and Reactive Oxygen Species

Cho

Seo

Kim

2011

Molecules and Cells

150

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In mammalian cells, reactive oxygen species (ROS) are produced via a variety of cellular oxidative processes, including the activity of NADPH oxidases (NOX), the activity of xanthine oxidases, the metabolism of arachidonic acid (AA) by lipoxygenases (LOX) and cyclooxygenases (COX), and the mitochondrial respiratory chain. Although NOX-generated ROS are the best characterized examples of ROS in mammalian cells, ROS are also generated by the oxidative metabolism (e.g., via LOX and COX) of AA that is released from the membrane phospholipids via the activity of cytosolic phospholipase A 2 (cPLA 2 ). Recently, growing evidence suggests that LOX-and COX-generated AA metabolites can induce ROS generation by stimulating NOX and that a potential signaling connection exits between the LOX/COX metabolites and NOX. In this review, we discuss the results of recent studies that report the generation of ROS by LOX metabolites, especially 5-LOX metabolites, via NOX stimulation. In particular, we have focused on the contribution of leukotriene B 4 (LTB 4 ), a potent bioactive eicosanoid that is derived from 5-LOX, and its receptors, BLT1 and BLT2, to NOX stimulation through a signaling mechanism that leads to ROS generation.

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Epidermis-Type Lipoxygenases

Cited by 15 publications

References 12 publications

Lipoxygenase metabolism: roles in tumor progression and survival

Lipoxygenase metabolism: roles in tumor progression and survival

Filaggrin in the frontline: role in skin barrier function and disease

Bioactive Lipoxygenase Metabolites Stimulation of NADPH Oxidases and Reactive Oxygen Species

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