Hypoxia increases cellular levels of phosphatidic acid and lysophospholipids in undifferentiated Caco-2 cells

Lipids. 2023 Mar;58(2):93-103. doi: 10.1002/lipd.12366. Epub 2023 Jan 28.

Abstract

Cancer cells are known to survive in a hypoxic microenvironment by altering their lipid metabolism as well as their energy metabolism. In this study, Caco-2 cells derived from human colon cancer, were found to have elevated intracellular levels of phosphatidic acid and its lysoform, lysophosphatidic acid (LPA), under hypoxic conditions. Our results suggested that the elevation of LPA in Caco-2 cells was mainly due to the combined increases in cellular levels of lysophosphatidylcholine and lysophosphatidylethanolamine by phospholipase A2 and subsequent hydrolysis to LPA by lysophospholipase D. We detected the Ca2+ -stimulated choline-producing activities toward exogenous lysophosphatidylcholines in whole Caco-2 cell homogenates, indicating their involvement in the LPA production in intact Caco-2 cells.

Keywords: glycerophosphodiesterase; liquid chromatography-tandem mass spectrometry; lysophosphatidic acid; lysophosphatidylcholine; lysophosphatidylethanolamine; phosphatidic acid.

MeSH terms

  • Caco-2 Cells
  • Humans
  • Lysophosphatidylcholines / metabolism
  • Lysophospholipids*
  • Phosphatidic Acids*

Substances

  • lysophosphatidic acid
  • Phosphatidic Acids
  • Lysophospholipids
  • Lysophosphatidylcholines