Role of the 12-lipoxygenase pathway in diabetes pathogenesis and complications

Abstract

12-lipoxygenase (12-LOX) is one of several enzyme isoforms responsible for the metabolism of arachidonic acid and other poly-unsaturated fatty acids to both pro-and anti-inflammatory lipid mediators. Mounting evidence has shown that 12-LOX plays a critical role in the modulation of inflammation at multiple checkpoints during diabetes development. Due to this, interventions to limit pro-inflammatory 12-LOX metabolites either by isoform-specific 12-LOX inhibition, or by providing specific fatty acid substrates via dietary intervention, has the potential to significantly

12(S)-HETE mediates diabetes-induced endothelial dysfunction by activating intracellular endothelial cell TRPV1

“…We here identify that elevated plasma concentrations of 12(S)-HETE directly link the hyperglycemic condition to vascular disease initiation in diabetes. We show that 12(S)-HpETE induces mitochondrial calcium increase and mitochondrial dysfunction characteristic of endothelial cells (27). In the cardiovascular system, a correlation of 12LOX activity with reduced nitric oxide bioavailability and a proatherogenic phenotype has been well characterized in mouse models of 12/15Lo knockout and overexpression (reviewed in Gleissner et al,ref.…”

Gigantol ameliorates CCl4-induced liver injury via preventing activation of JNK/cPLA2/12-LOX inflammatory pathway

“…Both platelet-type 12-LOX (Alox12) and leukocyte-type 12-LOX (Alox15) could catalyze the oxygenation of AA at the 12-position to form 12-HETE in mice 25 . The role of 12-LOX has been well demonstrated in the development of diabetes 20,26 . However, its role in liver injury is still vague.…”

“…In our study, NDGA inhibited the hepatic protein expression of 5-LOX, and platelet-, leukocyte-type 12-LOX activated by CCl 4 (Supplementary Figure S2). Baicalein could inhibit human platelet-type 12-LOX (Alox12) 12 , which shared 85% sequence homology with mouse platelet-type 12-LOX 26 . ML351 was originally a selective inhibitor for human 15-LOX-1 13 , which shared 73% sequence homology with mouse leukocyte-type 12-LOX www.nature.com/scientificreports/ (Alox15) 27 .…”

Plasma Amino Acids and Oxylipins As Potential Multi-Biomarkers for Predicting Diabetic Macular Edema

“…Recently, a number of studies have suggested a close association between diabetes and diabetes-related complications, and polyunsaturated fatty acids (PUFAs) metabolism [22][23][24] . For these reasons, the importance of lipid pro ling has emerged.…”