Prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis
1. We have previously demonstrated that nitric oxide (NO) triggers CD34⁺-derived megakaryocyte apoptosis. We here show that prostacyclin (PGI₂) inhibits PAPA/NO-induced megakaryocyte death detected by fluorescent microscopy and flow cytometry. 2. The cAMP-specific phosphodiesterase inhibitor, Ro 20...
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| Autores principales: | , , , , , , |
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| Formato: | Articulo |
| Lenguaje: | Inglés |
| Publicado: |
2005
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| Acceso en línea: | http://sedici.unlp.edu.ar/handle/10915/127155 |
| Aporte de: |
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I19-R120-10915-127155 |
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| record_format |
dspace |
| institution |
Universidad Nacional de La Plata |
| institution_str |
I-19 |
| repository_str |
R-120 |
| collection |
SEDICI (UNLP) |
| language |
Inglés |
| topic |
Ciencias Exactas Biología PGI₂ NO cAMP cGMP caspase |
| spellingShingle |
Ciencias Exactas Biología PGI₂ NO cAMP cGMP caspase Pozner, Roberto Gabriel Negrotto, Soledad D'Atri, Lina Paola Kotler, Mónica Lidia Lazzari, María Angela Gómez, Ricardo Martín Schattner, Mirta Prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis |
| topic_facet |
Ciencias Exactas Biología PGI₂ NO cAMP cGMP caspase |
| description |
1. We have previously demonstrated that nitric oxide (NO) triggers CD34⁺-derived megakaryocyte apoptosis. We here show that prostacyclin (PGI₂) inhibits PAPA/NO-induced megakaryocyte death detected by fluorescent microscopy and flow cytometry.
2. The cAMP-specific phosphodiesterase inhibitor, Ro 20-1724, and the permeable analog dibutyryl-cAMP also delayed apoptosis. PGI₂ effect was fully prevented when adenylyl cyclase activity was suppressed by SQ 22536, and partially reversed by the permeable protein kinase A inhibitor PKI 14-22 amide. ELISA showed that while both PGI₂ and NO alone or synergistically raised cAMP, only NO was able to increase intracellular cGMP levels.
3. Treatment of megakaryocytes with PGI₂ abolished both basal and NO-raised cGMP levels. Addition of 8-pCPT-cGMP or activation of soluble guanylyl cyclase by BAY 41-2272 induced cell death in a concentration-dependent manner, and ODQ, an inhibitor of guanylyl cyclase, prevented both PAPA/NO- or BAY 41-2272-induced apoptosis. Specific cGMP phosphodiesterase inhibition by Zaprinast or suppression of adenylyl cyclase by SQ 22536 enhanced the PAPA/NO proapoptotic effect.
4. PGI₂ completely inhibited NO-mediated generation and the increased activity of the cleaved form of caspase-3.
5. In conclusion, our results demonstrate that contrary to their well-known direct and synergistic inhibitory effects on platelets, PGI₂ and NO regulate opposite megakaryocyte survival responses through a delicate balance between intracellular cyclic nucleotide levels and caspase-3 activity control. |
| format |
Articulo Articulo |
| author |
Pozner, Roberto Gabriel Negrotto, Soledad D'Atri, Lina Paola Kotler, Mónica Lidia Lazzari, María Angela Gómez, Ricardo Martín Schattner, Mirta |
| author_facet |
Pozner, Roberto Gabriel Negrotto, Soledad D'Atri, Lina Paola Kotler, Mónica Lidia Lazzari, María Angela Gómez, Ricardo Martín Schattner, Mirta |
| author_sort |
Pozner, Roberto Gabriel |
| title |
Prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis |
| title_short |
Prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis |
| title_full |
Prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis |
| title_fullStr |
Prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis |
| title_full_unstemmed |
Prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis |
| title_sort |
prostacyclin prevents nitric oxide-induced megakaryocyte apoptosis |
| publishDate |
2005 |
| url |
http://sedici.unlp.edu.ar/handle/10915/127155 |
| work_keys_str_mv |
AT poznerrobertogabriel prostacyclinpreventsnitricoxideinducedmegakaryocyteapoptosis AT negrottosoledad prostacyclinpreventsnitricoxideinducedmegakaryocyteapoptosis AT datrilinapaola prostacyclinpreventsnitricoxideinducedmegakaryocyteapoptosis AT kotlermonicalidia prostacyclinpreventsnitricoxideinducedmegakaryocyteapoptosis AT lazzarimariaangela prostacyclinpreventsnitricoxideinducedmegakaryocyteapoptosis AT gomezricardomartin prostacyclinpreventsnitricoxideinducedmegakaryocyteapoptosis AT schattnermirta prostacyclinpreventsnitricoxideinducedmegakaryocyteapoptosis |
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Repositorios |
| _version_ |
1764820451340582913 |