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Review
. 2021 May 11;11(5):717.
doi: 10.3390/biom11050717.

Regulation of Tissue Inflammation by 12-Lipoxygenases

Abhishek Kulkarni  1 , Jerry L Nadler  2 , Raghavendra G Mirmira  1 , Isabel Casimiro  1
Affiliations
Review

Regulation of Tissue Inflammation by 12-Lipoxygenases

Abhishek Kulkarni et al. Biomolecules. .

Abstract

Lipoxygenases (LOXs) are lipid metabolizing enzymes that catalyze the di-oxygenation of polyunsaturated fatty acids to generate active eicosanoid products. 12-lipoxygenases (12-LOXs) primarily oxygenate the 12th carbon of its substrates. Many studies have demonstrated that 12-LOXs and their eicosanoid metabolite 12-hydroxyeicosatetraenoate (12-HETE), have significant pathological implications in inflammatory diseases. Increased level of 12-LOX activity promotes stress (both oxidative and endoplasmic reticulum)-mediated inflammation, leading to damage in these tissues. 12-LOXs are also associated with enhanced cellular migration of immune cells-a characteristic of several metabolic and autoimmune disorders. Genetic depletion or pharmacological inhibition of the enzyme in animal models of various diseases has shown to be protective against disease development and/or progression in animal models in the setting of diabetes, pulmonary, cardiovascular, and metabolic disease, suggesting a translational potential of targeting the enzyme for the treatment of several disorders. In this article, we review the role of 12-LOXs in the pathogenesis of several diseases in which chronic inflammation plays an underlying role.

Keywords: 12-LOXs; 12-lipoxygenases; 12/15-LOX; 12/15-lipoxygenase; eicosanoids; inflammation; lipoxygenases.

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Conflict of interest statement

J.L.N. and R.G.M. serve on the Scientific Advisory Board of Veralox Therapeutics.

Figures

Figure 1
Figure 1
Substrates and products of the 12-lipoxygenases.
Figure 2
Figure 2
Lipoxygenase orthologs.
Figure 3
Figure 3
The 12-Lipoxygenase Pathway.
Figure 4
Figure 4
12-Lipoxygenases play a role in a variety of inflammatory pathways and present a potential target for several inflammatory conditions.
See this image and copyright information in PMC

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