Functional and pathological roles of the 12- and 15-lipoxygenases

Abstract

The 12/15-lipoxygenase enzymes react with fatty acids producing active lipid metabolites that are involved in a number of significant disease states. The latter include type 1 and type 2 diabetes (and associated complications), cardiovascular disease, hypertension, renal disease, and the neurological conditions Alzheimer’s disease and Parkinson’s disease. A number of elegant studies over the last thirty years have contributed to unraveling the role that lipoxygenases play in chronic inflammation. The development of animal models with targeted gene deletions has led to a better understanding of the role that lipoxygenases play in various conditions. Selective inhibitors of the different lipoxygenase isoforms are an active area of investigation, and will be both an important research tool and a promising therapeutic target for treating a wide spectrum of human diseases.

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

“…Disappointingly, we conclude that the analysed SNPs in ALOX12, ALOX15, IL--6 or PPARG do not appear to make a major contribution to bone phenotypes at very advanced ages, while in young adult women ALOX15 and IL6 were associated with bone density and microarchitecture. Potential associations could be masked by gene--gene interactions (which were out with the scope of this study to address) or by the fact that both pro--and anti--inflammatory metabolites are generated by ALOX12/15 pathways and could modulate bone phenotypes [42].…”

α-Glucosidase inhibition, 15-lipoxygenase inhibition, and brine shrimp toxicity of extracts and isolated compounds fromTerminalia macropteraleaves

“…15-Lipoxygenase (15-LO) is an enzyme present in multiple systems and organs of the body that reacts with unsaturated fatty acids producing active lipid metabolites that are involved in a number of disease states such as cancer, psoriasis, atherosclerosis, and diabetes (both type 1 and 2) (Dobrian et al, 2011;Schneider & Bucar, 2005). For this reason, 15-LO has emerged as an attractive target for therapeutic intervention (Sadeghian et al, 2009).…”

Increased invasion of malignant gliomas after 15-LO-1 and HSV-tk/ganciclovir combination gene therapy

“…21,22 As a lipid-peroxidising enzyme 15-LO-1 utilizes linoleic and arachidonic acids as main substrates. 23 15-LO-1 metabolizes linoleic acid to 13-HODE, which has been shown to have anti-angiogenic/antitumorogenic properties. 24 On the contrary, the metabolism of arachidonic acid by 15-LO-1 results in 15-S-hydroxyeicosatetraenoic acid and 12-hydroxyeicosatetraenoic acid.…”

“…24 On the contrary, the metabolism of arachidonic acid by 15-LO-1 results in 15-S-hydroxyeicosatetraenoic acid and 12-hydroxyeicosatetraenoic acid. 23 Of these metabolites, 12-hydroxyeicosatetraenoic acid has shown to have pro-tumorigenic/ pro-metastatic properties. 25,26 It would be interesting to evaluate, whether a change in substrate availability for 15-LO-1 can be detected within the gliomas, resulting in an increase of 12-hydroxy-eicosatetraenoic acid, thereby triggering tumor cell invasion and metastasis.…”