Abstract
Nitric oxide (·NO) can be produced within the lung, and recently inhaled nitric oxide has been used as a therapeutic agent. Peroxynitrite1 (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.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology - Lung Cellular and Molecular Physiology |
| Volume | 274 |
| Issue number | 1 18-1 |
| Publication status | Published - Jan 1998 |
| Externally published | Yes |
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Keywords
- Apoptosis
- Endothelium
- Superoxide
- Type II epithelium
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Cell Biology
- Physiology
- Physiology (medical)
Cite this
Nitric oxide and peroxynitrite-mediated pulmonary cell death. / Gow, Andrew J.; Thom, Stephen R.; Ischiropoulos, Harry.
In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 274, No. 1 18-1, 01.1998.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nitric oxide and peroxynitrite-mediated pulmonary cell death
AU - Gow, Andrew J.
AU - Thom, Stephen R.
AU - Ischiropoulos, Harry
PY - 1998/1
Y1 - 1998/1
N2 - Nitric oxide (·NO) can be produced within the lung, and recently inhaled nitric oxide has been used as a therapeutic agent. Peroxynitrite1 (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.
AB - Nitric oxide (·NO) can be produced within the lung, and recently inhaled nitric oxide has been used as a therapeutic agent. Peroxynitrite1 (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.
KW - Apoptosis
KW - Endothelium
KW - Superoxide
KW - Type II epithelium
UR - http://www.scopus.com/inward/record.url?scp=0031885274&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031885274&partnerID=8YFLogxK
M3 - Article
VL - 274
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
SN - 1040-0605
IS - 1 18-1
ER -