TY - JOUR
T1 - Peroxynitrite Causes Energy Depletion and Increases Permeability via Activation of Poly (ADP-Ribose) Synthetase in Pulmonary Epithelial Cells
AU - Szabó, Csaba
AU - Saunders, Christine
AU - O'Connor, Michael
AU - Salzman, Andrew L.
PY - 1997
Y1 - 1997
N2 - Recent studies show that peroxynitrite is a potent trigger of DNA strand breakage, which in turn activates the nuclear repair enzyme poly (ADP-ribose) synthetase (PARS), resulting in a cellular energy deficit. Here we present evidence that treatment of A549 human pulmonary epithelial cells with peroxynitrite (1 mM) results in ADP-ribosylation, NAD+ depletion, inhibition of mitochondrial respiration, and increased epithelial paracellular permeability. The PARS inhibitor 3-aminobenzamide (1 mM) provided a significant, partial protection against the energetic and functional changes. Similarly, inhibition of PARS activity by 3-aminobenzamide reduced the peroxynitrite-induced suppression of mitochondrial respiration in BEAS-2B human bronchial epithelial cells. Thus, PARS activation and energy depletion represents one of the pathways of peroxynitrite-mediated epithelial toxicity. Inhibition of PARS may improve cellular energy homeostasis in pathophysiologic conditions associated with peroxynitrite generation.
AB - Recent studies show that peroxynitrite is a potent trigger of DNA strand breakage, which in turn activates the nuclear repair enzyme poly (ADP-ribose) synthetase (PARS), resulting in a cellular energy deficit. Here we present evidence that treatment of A549 human pulmonary epithelial cells with peroxynitrite (1 mM) results in ADP-ribosylation, NAD+ depletion, inhibition of mitochondrial respiration, and increased epithelial paracellular permeability. The PARS inhibitor 3-aminobenzamide (1 mM) provided a significant, partial protection against the energetic and functional changes. Similarly, inhibition of PARS activity by 3-aminobenzamide reduced the peroxynitrite-induced suppression of mitochondrial respiration in BEAS-2B human bronchial epithelial cells. Thus, PARS activation and energy depletion represents one of the pathways of peroxynitrite-mediated epithelial toxicity. Inhibition of PARS may improve cellular energy homeostasis in pathophysiologic conditions associated with peroxynitrite generation.
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U2 - 10.1165/ajrcmb.16.2.9032115
DO - 10.1165/ajrcmb.16.2.9032115
M3 - Article
C2 - 9032115
AN - SCOPUS:0031066766
SN - 1044-1549
VL - 16
SP - 105
EP - 109
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 2
ER -