AJP - Lung Cellular and Molecular Physiology, Vol 269, Issue 1 59-L64, Copyright © 1995 by American Physiological Society
Inhibition of poly(ADP-ribose) polymerase preserves surfactant synthesis after hydrogen peroxide exposure
B. B. Hudak, J. Tufariello, J. Sokolowski, C. Maloney and B. A. Holm
Department of Pediatrics, State University of New York at Buffalo, USA.
Exposure to hydrogen peroxide (H2O2) decreases phosphatidylcholine (PC)
synthesis in rabbit type II pneumocytes. Activation of poly(ADP-ribose)
polymerase (PARP) may play a role in this process. Exposure of type II
pneumocytes to H2O2 resulted in a 53% decrease in the rate of incorporation
of [3H]choline into PC (P < 0.001). Cell NAD and ATP levels were
decreased by 52% (P < 0.001) and 39% (P < 0.01), respectively,
without significant changes in cell viability. Exposure to H2O2 also
resulted in a 52% (P < 0.05) increase in the activity of PARP.
Preincubation of type II cells with inhibitors of PARP (nicotinamide;
3-aminobenzamide) before H2O2 exposure prevented the increase in PARP
activity, and blocked the decreases in ATP, NAD, and rate of PC synthesis.
These results suggest that the energy depletion associated with activation
of PARP contributes to the effects of oxidant stress on type II cell
metabolic function and may be ameliorated by pharmacological agents in
vitro.
