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Lipid A stimulates phospholipase D activity in rat mesangial cells via a G-protein

W E Harrris1, S L Bursten

  • 1Neurochemistry Laboratory, Veterans Affairs Medical Center, Seattle, WA 98108.

The Biochemical Journal
|February 1, 1992
PubMed

Insights

Bacterial endotoxin Lipid A activates enzymes in mesangial cells, altering lipid metabolism. This study reveals a G-protein-dependent pathway involving phospholipase D and PA phosphohydrolase in response to Lipid A.

Area of Science:

  • Cell Biology
  • Biochemistry
  • Immunology

Background:

  • Mesangial cells (MC) play a role in kidney function and immune responses.
  • Bacterial endotoxins like Lipid A can trigger cellular signaling pathways.
  • Lipid metabolism is crucial for cellular function and signaling.

Purpose of the Study:

  • To investigate the effects of Lipid A on lipid metabolism in mesangial cells.
  • To identify the enzymes and signaling pathways involved in the MC response to Lipid A.
  • To elucidate the role of G-proteins in Lipid A-induced lipid changes.

Main Methods:

  • Mesangial cells and microsomes were pre-labeled with [3H]glycerol.
  • Stimulation with bacterial endotoxin Lipid A and sodium fluoride (NaF).
  • Analysis of lipid products using radioactive labeling and mass measurements, including guanosine 5'-[gamma-thio]triphosphate activation.

Main Results:

  • Lipid A stimulation led to the hydrolysis of phosphatidylethanolamine (PE) to phosphatidic acid (PA) and subsequent dephosphorylation to 1,2-diacylglycerol (DAG).
  • The identified phospholipase D showed a preference for unsaturated acyl side chains in PE.
  • G-protein activation mimicked Lipid A effects, suggesting a G-protein-dependent mechanism.

Conclusions:

  • Lipid A concurrently activates a PE-directed phospholipase D and a PA phosphohydrolase in mesangial cells.
  • This activation is dependent on G-protein signaling pathways.
  • The findings provide insights into the molecular mechanisms of endotoxin-induced lipid metabolism changes in MCs.

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