Hypoxia inhibits myosin phosphatase in pulmonary arterial smooth muscle cells: role of Rho-kinase.
Am J Respir Cell Mol Biol
; 29(4): 465-71, 2003 Oct.
Article
in En
| MEDLINE
| ID: mdl-12714374
ABSTRACT
Rho-kinase was recently found to phosphorylate the myosin-binding subunit (MBS) of myosin phosphatase (MP) and to regulate MP activity. Although myosin light chain (MLC) phosphorylation in pulmonary arterial smooth muscle cells (PASMCs) is thought to be the cellular/molecular basis for hypoxic pulmonary vasoconstriction (HPV), very little is known about the role that Rho-kinase/MP plays in HPV. Rat PASMCs were cultured and made hypoxic (PO2 = 23 +/- 2 mm Hg). Cells exposed to normoxia (PO2 approximately 148 mm Hg) served as controls. PASMCs exposed to hypoxia showed a significant increase in MLC and MBS phosphorylation, and a significant decrease in MP activity. Rho-kinase inhibitors (HA1077 or Y-27632) blocked hypoxia-induced MP inactivation and inhibited the hypoxia-induced MLC phosphorylation. Hypoxia was also found to induce stress fiber formation and actin polymerization in cultured PASMCs. In summary, these data show that MP inhibition in PASMCs is linked to activation of Rho-kinase, and that hypoxia inhibits the MP signaling pathway via Rho-kinase.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pulmonary Artery
/
Vasoconstriction
/
Protein Serine-Threonine Kinases
/
Phosphoprotein Phosphatases
/
Hypoxia
/
Muscle, Smooth, Vascular
Limits:
Animals
Language:
En
Journal:
Am J Respir Cell Mol Biol
Journal subject:
BIOLOGIA MOLECULAR
Year:
2003
Document type:
Article
Affiliation country:
United States