S-Nitrosothiols signal hypoxia-mimetic vascular pathology
J. Clin. Invest. Lisa A. Palmer, et al. 117:2592 doi:10.1172/JCI29444 [
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Figure 4SNOAC recapitulates in primary pulmonary arterial endothelial cells the hypoxia-mimetic whole-lung effect of chronic NAC administration on Sp3 expression in vivo. (
A) One micromolar SNOAC, but not 50 μM NAC, treatment (4 hours each) increased intracellular
S-nitrosothiol levels (assayed by Cu/cysteine chemiluminescence; ref.
11) in primary murine pulmonary endothelial cells (*
P < 0.05 compared with SNOAC treatment). (
B) Immunoblot showing increased Sp3 expression relative to MAPK in the whole-lung homogenates of mice treated for 3 weeks with 10 mg/ml NAC but not in those of control mice. By densitometry, this increase was significant (
P < 0.01). (
C) Paradoxically, however, NAC (50 μM; 4 hours) did not increase Sp3 expression relative to β-actin in primary murine pulmonary endothelial cells in vitro, while both SNOAC (1 μM; 4 hours) and hypoxia (10%; 4 hours) did.