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Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells
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| Zeitschriftentitel: | American Journal of Physiology-Cell Physiology |
|---|---|
| Personen und Körperschaften: | , |
| In: | American Journal of Physiology-Cell Physiology, 282, 2002, 2, S. C395-C402 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Physiological Society
|
| Schlagwörter: |
| author_facet |
Cooke, Christy-Lynn M. Davidge, Sandra T. Cooke, Christy-Lynn M. Davidge, Sandra T. |
|---|---|
| author |
Cooke, Christy-Lynn M. Davidge, Sandra T. |
| spellingShingle |
Cooke, Christy-Lynn M. Davidge, Sandra T. American Journal of Physiology-Cell Physiology Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells Cell Biology Physiology |
| author_sort |
cooke, christy-lynn m. |
| spelling |
Cooke, Christy-Lynn M. Davidge, Sandra T. 0363-6143 1522-1563 American Physiological Society Cell Biology Physiology http://dx.doi.org/10.1152/ajpcell.00295.2001 <jats:p>Peroxynitrite, a marker of oxidative stress, is elevated in conditions associated with vascular endothelial cell dysfunction, such as atherosclerosis, preeclampsia, and diabetes. However, the effects of peroxynitrite on endothelial cell function are not clear. The endothelium-derived enzymes nitric oxide synthase (NOS) and prostaglandin H synthase (PGHS) mediate vascular reactivity and contain oxidant-sensitive isoforms (iNOS and PGHS-2) that can be induced by nuclear factor (NF)-κB activation. We investigated the effect(s) of peroxynitrite on NOS and PGHS pathways in endothelial cells. We hypothesized that peroxynitrite will increase levels of iNOS and PGHS-2 through activation of NF-κB. Western immunoblots of endothelial cells show that 3-morpholinosydnonimine (SIN-1; 0.5 mM), a peroxynitrite donor, increased iNOS protein mass, which can be inhibited by pyrroline dithiocarbamate (an NF-κB inhibitor) (167 ± 24.2 vs. 78 ± 19%, P < 0.05, n = 6). SIN-1 treatment also significantly increased NF-κB translocation into endothelial cell nuclei (135 ± 10%, P < 0.05). Endothelial NOS, PGHS-1, and PGHS-2 protein levels were not altered by SIN-1. However, prostacyclin synthase protein mass, but not mRNA, was significantly reduced in SIN-1-treated endothelial cells (78 ± 8.9%, P < 0.05). Our results illustrate novel mechanisms through which peroxynitrite may modulate vascular endothelial function.</jats:p> Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells American Journal of Physiology-Cell Physiology |
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| title |
Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_unstemmed |
Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_full |
Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_fullStr |
Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_full_unstemmed |
Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_short |
Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_sort |
peroxynitrite increases inos through nf-κb and decreases prostacyclin synthase in endothelial cells |
| topic |
Cell Biology Physiology |
| url |
http://dx.doi.org/10.1152/ajpcell.00295.2001 |
| publishDate |
2002 |
| physical |
C395-C402 |
| description |
<jats:p>Peroxynitrite, a marker of oxidative stress, is elevated in conditions associated with vascular endothelial cell dysfunction, such as atherosclerosis, preeclampsia, and diabetes. However, the effects of peroxynitrite on endothelial cell function are not clear. The endothelium-derived enzymes nitric oxide synthase (NOS) and prostaglandin H synthase (PGHS) mediate vascular reactivity and contain oxidant-sensitive isoforms (iNOS and PGHS-2) that can be induced by nuclear factor (NF)-κB activation. We investigated the effect(s) of peroxynitrite on NOS and PGHS pathways in endothelial cells. We hypothesized that peroxynitrite will increase levels of iNOS and PGHS-2 through activation of NF-κB. Western immunoblots of endothelial cells show that 3-morpholinosydnonimine (SIN-1; 0.5 mM), a peroxynitrite donor, increased iNOS protein mass, which can be inhibited by pyrroline dithiocarbamate (an NF-κB inhibitor) (167 ± 24.2 vs. 78 ± 19%, P < 0.05, n = 6). SIN-1 treatment also significantly increased NF-κB translocation into endothelial cell nuclei (135 ± 10%, P < 0.05). Endothelial NOS, PGHS-1, and PGHS-2 protein levels were not altered by SIN-1. However, prostacyclin synthase protein mass, but not mRNA, was significantly reduced in SIN-1-treated endothelial cells (78 ± 8.9%, P < 0.05). Our results illustrate novel mechanisms through which peroxynitrite may modulate vascular endothelial function.</jats:p> |
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| author | Cooke, Christy-Lynn M., Davidge, Sandra T. |
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| description | <jats:p>Peroxynitrite, a marker of oxidative stress, is elevated in conditions associated with vascular endothelial cell dysfunction, such as atherosclerosis, preeclampsia, and diabetes. However, the effects of peroxynitrite on endothelial cell function are not clear. The endothelium-derived enzymes nitric oxide synthase (NOS) and prostaglandin H synthase (PGHS) mediate vascular reactivity and contain oxidant-sensitive isoforms (iNOS and PGHS-2) that can be induced by nuclear factor (NF)-κB activation. We investigated the effect(s) of peroxynitrite on NOS and PGHS pathways in endothelial cells. We hypothesized that peroxynitrite will increase levels of iNOS and PGHS-2 through activation of NF-κB. Western immunoblots of endothelial cells show that 3-morpholinosydnonimine (SIN-1; 0.5 mM), a peroxynitrite donor, increased iNOS protein mass, which can be inhibited by pyrroline dithiocarbamate (an NF-κB inhibitor) (167 ± 24.2 vs. 78 ± 19%, P < 0.05, n = 6). SIN-1 treatment also significantly increased NF-κB translocation into endothelial cell nuclei (135 ± 10%, P < 0.05). Endothelial NOS, PGHS-1, and PGHS-2 protein levels were not altered by SIN-1. However, prostacyclin synthase protein mass, but not mRNA, was significantly reduced in SIN-1-treated endothelial cells (78 ± 8.9%, P < 0.05). Our results illustrate novel mechanisms through which peroxynitrite may modulate vascular endothelial function.</jats:p> |
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| spelling | Cooke, Christy-Lynn M. Davidge, Sandra T. 0363-6143 1522-1563 American Physiological Society Cell Biology Physiology http://dx.doi.org/10.1152/ajpcell.00295.2001 <jats:p>Peroxynitrite, a marker of oxidative stress, is elevated in conditions associated with vascular endothelial cell dysfunction, such as atherosclerosis, preeclampsia, and diabetes. However, the effects of peroxynitrite on endothelial cell function are not clear. The endothelium-derived enzymes nitric oxide synthase (NOS) and prostaglandin H synthase (PGHS) mediate vascular reactivity and contain oxidant-sensitive isoforms (iNOS and PGHS-2) that can be induced by nuclear factor (NF)-κB activation. We investigated the effect(s) of peroxynitrite on NOS and PGHS pathways in endothelial cells. We hypothesized that peroxynitrite will increase levels of iNOS and PGHS-2 through activation of NF-κB. Western immunoblots of endothelial cells show that 3-morpholinosydnonimine (SIN-1; 0.5 mM), a peroxynitrite donor, increased iNOS protein mass, which can be inhibited by pyrroline dithiocarbamate (an NF-κB inhibitor) (167 ± 24.2 vs. 78 ± 19%, P < 0.05, n = 6). SIN-1 treatment also significantly increased NF-κB translocation into endothelial cell nuclei (135 ± 10%, P < 0.05). Endothelial NOS, PGHS-1, and PGHS-2 protein levels were not altered by SIN-1. However, prostacyclin synthase protein mass, but not mRNA, was significantly reduced in SIN-1-treated endothelial cells (78 ± 8.9%, P < 0.05). Our results illustrate novel mechanisms through which peroxynitrite may modulate vascular endothelial function.</jats:p> Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells American Journal of Physiology-Cell Physiology |
| spellingShingle | Cooke, Christy-Lynn M., Davidge, Sandra T., American Journal of Physiology-Cell Physiology, Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells, Cell Biology, Physiology |
| title | Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_full | Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_fullStr | Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_full_unstemmed | Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_short | Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| title_sort | peroxynitrite increases inos through nf-κb and decreases prostacyclin synthase in endothelial cells |
| title_unstemmed | Peroxynitrite increases iNOS through NF-κB and decreases prostacyclin synthase in endothelial cells |
| topic | Cell Biology, Physiology |
| url | http://dx.doi.org/10.1152/ajpcell.00295.2001 |