Portal de Periódicos da CAPES

Nitric oxide and peroxynitrite-mediated pulmonary cell death

1998; American Physical Society; Volume: 274; Issue: 1 Linguagem: Inglês

10.1152/ajplung.1998.274.1.l112

1522-1504

Andrew J. Gow, Stephen R. Thom, Harry Ischiropoulos,

Neutrophil, Myeloperoxidase and Oxidative Mechanisms

Nitric oxide (⋅ NO) can be produced within the lung, and recently inhaled nitric oxide has been used as a therapeutic agent. Peroxynitrite 1 (ONOO − ), the product of the nearly diffusion-limited reaction between ⋅ NO and superoxide, may represent the proximal reactive species mediating ⋅ NO injury to pulmonary cells. To investigate the physiological and pathological reactivities of ⋅ NO and ONOO − at the molecular and cellular levels, bovine pulmonary artery endothelial cells (BPAEC) and rat type II epithelial cells were exposed to ⋅ NO (0.01–2.5 μM/min for 2 h) generated by spermine-NONOate and papa-NONOate and to the same fluxes of ONOO − generated by 1,3-morpholinosydnonimine (SIN-1). Exposure to SIN-1 resulted in cellular injury and death in both cell types. Epithelial cells displayed a concentration-dependent loss of cellular viability within 8 h of exposure. In contrast, BPAEC loss of cellular viability was evident after 18 h postexposure. Events preceding cell death in BPAEC include depolarization of the mitochondrial membrane, evident as early as 6 h postexposure, loss of cellular redox activity at 16 h, and DNA fragmentation detected by in situ staining at 18 h after exposure. Exposure of BPAEC to ⋅ NO did not affect the cellular viability, but type II cells were injured in a manner similar to ONOO − exposure. ⋅ NO-mediated cellular injury within type II cells was reduced by preincubation with N-acetylcysteine. The data imply that the pathological and physiological effects of ⋅ NO may be regulated by its reactions with superoxide and reduced thiols.