8-Isoprostane-induced endothelin-1 production by infant rat pulmonary artery smooth muscle cells is mediated by Rho-kinase
| Autor: | Crystal Kantores, Soojin Yi, Judy Cabacungan, Robert P. Jankov, A. Keith Tanswell, Rosetta Belcastro |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
medicine.medical_specialty
RHOA Cell Culture Techniques Protein Serine-Threonine Kinases Pulmonary Artery Mitogen-activated protein kinase kinase Biology Dinoprost Biochemistry Muscle Smooth Vascular Rats Sprague-Dawley Thromboxane receptor chemistry.chemical_compound Physiology (medical) Internal medicine medicine Animals Protease Inhibitors ASK1 Rho-associated protein kinase Calcimycin Protein Kinase C rho-Associated Kinases Endothelin-1 Akt/PKB signaling pathway Intracellular Signaling Peptides and Proteins Immunohistochemistry Endothelin 1 Rats Enzyme Activation Y-27632 Endocrinology chemistry 15-Hydroxy-11 alpha 9 alpha-(epoxymethano)prosta-5 13-dienoic Acid biology.protein |
| Zdroj: | Free Radical Biology and Medicine. 41:942-949 |
| ISSN: | 0891-5849 |
| DOI: | 10.1016/j.freeradbiomed.2006.05.035 |
| Popis: | We have reported that 8-isoprostane stimulated the production of endothelin (ET)-1, a potent vasoconstrictor and critical mediator of chronic pulmonary hypertension, by infant rat pulmonary artery smooth muscle cells (PASMCs), through stimulation of the thromboxane A2 receptor. The aim of this study was to examine the contribution of putative downstream intracellular mediators of thromboxane A2 receptor stimulation to this effect. PASMCs from infant rats were treated with calcium ionophore (A23187), 8-isoprostane, or 8-isoprostane together with inhibitors of tyrosine kinase, protein kinase C, phosphatidylinositol 3-kinase, mitogen-activated protein kinases, or Rho-kinases (ROCK). A23187 had no effect on ET-1 production, excluding raised intracellular Ca2+ as a major contributor. Increased ET-1 production induced by 8-isoprostane was significantly attenuated by the ROCK inhibitors Y-27632 and hydroxyfasudil, but not by inhibitors of the other pathways. 8-Isoprostane also increased membrane binding of RhoA, a major determinant of ROCK activity, and ROCK-II expression through the protein kinase C pathway. These data indicate that the RhoA/ROCK pathway mediates increased ET-1 production by PASMCs, which we speculate may at least partly explain the beneficial effects of both antioxidants and ROCK inhibitors in animal models of chronic pulmonary hypertension. |
| Databáze: | OpenAIRE |
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