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Roles of lipid-modulating enzymes diacylglycerol kinase and cyclooxygenase under pathophysiological conditions

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Abstract

Lipid not only represents a constituent of the plasma membrane, but also plays a pivotal role in intracellular signaling. Lipid-mediated signaling system is strictly regulated by several enzymes, which act at various steps of the lipid metabolism. Under pathological conditions, prolonged or insufficient activation of this system results in dysregulated signaling, leading to diseases such as cancer or metabolic syndrome. Of the lipid-modulating enzymes, diacylglycerol kinase (DGK) and cyclooxygenase (COX) are intimately involved in the signaling system. DGK consists of a family of enzymes that phosphorylate a second messenger diacylglycerol (DG) to produce phosphatidic acid (PA). Both DG and PA are known to activate signaling molecules such as protein kinase C. COX catalyzes the committed step in prostanoid biosynthesis, which involves the metabolism of arachidonic acid to produce prostaglandins. Previous studies have shown that the DGK and COX are engaged in a number of pathological conditions. This review summarizes the functional implications of these two enzymes in ischemia, liver regeneration, vascular events, diabetes, cancer and inflammation.

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Acknowledgments

The author thanks Prof. Kaoru Goto, Yamagata University, for helpful discussions on DGK and critical reading of the manuscript. The author also thanks Prof. Ichiro Wakabayashi, Hyogo College of Medicine, for valuable discussions on COX. Finally, the author thanks Drs. Matthew K Topham and Diana Stafforini, University of Utah, for helpful suggestions and technical advice on cancer biology.

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  1. Department of Anatomy and Cell Biology, Yamagata University School of Medicine, 2-2-2 Iida-nishi, Yamagata City, Yamagata, 990-9585, Japan

    Tomoyuki Nakano

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Nakano, T. Roles of lipid-modulating enzymes diacylglycerol kinase and cyclooxygenase under pathophysiological conditions. Anat Sci Int 90, 22–32 (2015). https://doi.org/10.1007/s12565-014-0265-7

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