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PI3K p110α isoform-dependent Rho GTPase Rac1 activation mediates H2S-promoted endothelial cell migration via actin cytoskeleton reorganization.
- Source :
-
PloS one [PLoS One] 2012; Vol. 7 (9), pp. e44590. Date of Electronic Publication: 2012 Sep 07. - Publication Year :
- 2012
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Abstract
- Hydrogen sulfide (H(2)S) is now considered as the third gaseotransmitter, however, the signaling pathways that modulate the biomedical effect of H(2)S on endothelial cells are poorly defined. In the present study, we found in human endothelial cells that H(2)S increased cell migration rates and induced a marked reorganization of the actin cytoskeleton, which was prevented by depletion of Rac1. Pharmacologic inhibiting vascular endothelial growth factor receptor (VEGFR) and phosphoinositide 3-kinase (PI3K) both blunted the activation of Rac1 and the promotion of cell migration induced by H(2)S. Moreover, H(2)S-induced Rac1 activation was selectively dependent on the presence of the PI3K p110α isoform. Activated Rac1 by H(2)S thus in turn resulted in the phosphorylation of the F-actin polymerization modulator, cofilin. Additionally, inhibiting of extracellular signal-regulated kinase (ERK) decreased the augmented cell migration rate by H(2)S, but had no effect on Rac1 activation. These results indicate that Rac1 conveys the H(2)S signal to microfilaments inducing rearrangements of actin cytoskeleton that regulates cell migration. VEGFR-PI3K was found to be upstream pathway of Rac1, while cofilin acted as a downstream effector of Rac1. ERK was also shown to be involved in the action of H(2)S on endothelial cell migration, but independently of Rac1.
- Subjects :
- Base Sequence
DNA Primers
Endothelium, Vascular cytology
Endothelium, Vascular metabolism
Humans
RNA, Small Interfering
Reverse Transcriptase Polymerase Chain Reaction
Actins metabolism
Cell Movement drug effects
Cytoskeleton metabolism
Endothelium, Vascular drug effects
Hydrogen Sulfide pharmacology
Isoenzymes metabolism
Phosphatidylinositol 3-Kinases metabolism
rac1 GTP-Binding Protein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 7
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 22970259
- Full Text :
- https://doi.org/10.1371/journal.pone.0044590