Mammalian lipoxygenases and their biological relevance

Abstract

Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders.

Lipoxin and resolvin biosynthesis is dependent on 5‐lipoxygenase activating protein

“…So far, we were not able to detect LX in these cells. Murine 12/15-LO (mALOX15), in contrast to human 15-LO-1 (hALOX15), is a primarily 12-lipoxygenating enzyme (40). Therefore, comparable to PMNL/platelet coincubations, 5-LO-derived LTA 4 is probably converted to LXA 4.…”

STAT-Dependent Upregulation of 12/15-Lipoxygenase Contributes to Neuronal Injury after Stroke

“…[33][34][35] Consequently, it is subject to several layers of regulation including transcriptional, translational, and posttranslational control mechanisms that keep the enzyme activity in check. 36 After a catastrophic event such as an ischemic stroke, this regulatory network breaks down, leading to increased 12/15-LOX protein levels.…”

Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction

“…These 5-LOX products bind G-protein coupled receptors (GPCRs), in particular B-LT 1 and B-LT 2 receptors for LTB 4 and Cys-LT 1 and Cys-LT 2 for LTC 4 and LTD 4 (Back et al, 2014). On the other hand, 15-LOX exists in two isoforms: 15-LOX-1 and 15-LOX-2, which transform arachidonic acid into 15(S)-HETE (Kuhn et al, 2015). 12/15-LOX is the murine ortholog of human 15-LOX-1 (Kuhn et al, 2015).…”

“…On the other hand, 15-LOX exists in two isoforms: 15-LOX-1 and 15-LOX-2, which transform arachidonic acid into 15(S)-HETE (Kuhn et al, 2015). 12/15-LOX is the murine ortholog of human 15-LOX-1 (Kuhn et al, 2015). The physiologic role of 15-LOX is dependent on the context in which it is expressed, but this pathway is essential for the formation of products able to antagonize and properly resolve inflammatory responses (see Section 4.1.3).…”