Palmitic acid- and/or palmitoleic acid-containing phosphatidic acids are generated by diacylglycerol kinase α in starved Jurkat T cells.

Abstract

Diacylglycerol kinase (DGK) α enhances the proliferation of melanoma and hepatocellular carcinoma cells whereas, in contrast, DGKα induces a nonproliferative state in T cells. We previously found that DGKα produces palmitic acid (16:0)-containing PA species, such as 16:0/16:0- and 16:0/18:0-PA, in melanoma cells under serum-starved (nonproliferative) conditions. In the present study, we identified the PA species generated by DGKα in T cells under serum-starved (nonproliferative) conditions. We found that serum starvation markedly increased the levels of many PA species, such as 14:1/16:1-, 14:0/16:1-, 14:0/16:0-, 16:1/16:2-, 16:1/16:1-, 16:0/16:1-, 16:0/16:0-, 16:1/18:2-, 16:1/18:1-, 16:0/18:1-, 16:0/18:0-, 18:1/18:2-, 18:1/18:1- and 18:0/18:1-PA, in Jurkat T cells. In lysates from serum-starved Jurkat T cells, DGKα activity, which was Ca2+-dependent and sensitive to a DGKα-specific inhibitor (CU-3), was substantially increased, indicating its activation. Moreover, CU-3 (1-10 μM) significantly reduced the amounts of palmitic acid- and/or palmitoleic acid (16:1)-containing PA species, such as 14:1/16:1-, 14:0/16:1-, 14:0/16:0-, 16:1/16:2-, 16:1/16:1-, 16:0/16:1-, 16:0/16:0-, 16:0/18:1- and 16:0/18:0-PA, which were increased by serum starvation. These results indicate that DGKα generates different PA species in starved melanoma cells (palmitic acid-containing PA species) and T cells (palmitic acid- and/or palmitoleic acid (16:1)-containing PA species). Therefore, the differences in the PA molecular species may account for the opposing functions of DGKα in melanoma and T cells.

• Authors: Yuki Murakami, Chiaki Murakami, Fumi Hoshino, Qiang Lu, Rino Akiyama, Atsumi Yamaki, Daisuke Takahashi, Fumio Sakane
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 525 Issue 4 Pg. 1054-1060 (05 14 2020) ISSN: 1090-2104 [Electronic] United States
• PMID: 32184022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• 5-(3-(2-furyl)prop-2-enylidene)-3-((phenylsulfonyl)amino)-2-thioxo-1,3-thiazolidin-4-one
• Fatty Acids, Monounsaturated
• Phosphatidic Acids
• Sulfonamides
• palmitoleic acid
• Palmitic Acid
• Rhodanine
• Diacylglycerol Kinase
• Calcium

Topics

• Calcium (metabolism)
• Cell Proliferation
• Chromatography, Liquid
• Diacylglycerol Kinase (antagonists & inhibitors, metabolism)
• Fatty Acids, Monounsaturated (chemistry, metabolism)
• Humans
• Jurkat Cells
• Melanoma (chemistry, enzymology, metabolism)
• Palmitic Acid (chemistry, metabolism)
• Phosphatidic Acids (chemistry, metabolism)
• Rhodanine (analogs & derivatives, pharmacology)
• Sulfonamides (pharmacology)
• T-Lymphocytes (chemistry, drug effects, enzymology, metabolism)
• Tandem Mass Spectrometry