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Lipid ozonation products activate phospholipases A2, C, and D
R M Kafoury1, W A Pryor, G L Squadrito
1Department of Environmental Health Sciences, Tulane University Medical Center, New Orleans, Louisiana 70112, USA.
Toxicology and Applied Pharmacology
|July 7, 1998
Summary
Ozone exposure triggers lipid ozonation products (LOP) that activate phospholipase A2 (PLA2), C (PLC), and D (PLD) in airway cells. These activated enzymes may contribute to lung inflammation from ozone exposure.
Area of Science:
- Cell Biology
- Toxicology
- Biochemistry
Background:
- Ozone exposure is known to activate phospholipases A2 (PLA2), C (PLC), and D (PLD) in airway epithelial cells.
- Due to ozone's reactivity, its toxicity is thought to be mediated by lipid ozonation products (LOP) formed from reactions with lipids in the lung.
- This study investigates the role of LOP in activating phospholipases in airway epithelial cells.
Purpose of the Study:
- To determine if lipid ozonation products (LOP) activate phospholipase A2 (PLA2), C (PLC), and D (PLD) in human bronchial epithelial cells.
- To identify the specific LOP responsible for activating these enzymes.
- To compare the effects of LOP with other oxidants on phospholipase activity.
Main Methods:
- Cultured human bronchial epithelial cells (BEAS-2B) were exposed to LOP generated from ozonized 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC).
- Activities of PLA2, PLC, and PLD were measured.
- The specific PLA2 isoform responsible for arachidonic acid release was characterized.
- Comparison of LOP effects with those of hydrogen peroxide (H2O2), tert-butyl hydroperoxide (t-BOOH), and 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH).
Main Results:
- Specific LOP derivatives, including 9-oxononanoyl (PC-ALD), 9-hydroxy-9-hydroperoxynonanoyl (PC-HHP), and POPC-OZ, dose-dependently activated PLA2.
- Cytosolic PLA2 (cPLA2) was identified as the primary isoform for arachidonic acid release.
- PLC activation was induced by hydroxyhydroperoxide derivatives (PC-HHP and HHP-C9).
- PLD activity was also induced by LOP.
- Other oxidants (H2O2, t-BOOH, AAPH) showed differential effects on phospholipase activation compared to LOP.
Conclusions:
- Biologically relevant concentrations of LOP activate PLA2, PLC, and PLD in airway epithelial cells.
- These activated phospholipases are likely involved in the inflammatory responses observed during ozone exposure.
- LOP-mediated phospholipase activation represents a key mechanism in ozone-induced lung toxicity.