| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
and RhoA Cross-talk
1 Department of Pharmacology, Rush University Medical Center, Chicago, IL, USA
2 Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA
3 Department of Medicine, John H. Stroger Hospital of Cook County, Chicago, IL, USA
4 Research Service, Stratton Veterans Affairs Medical Center, Albany, NY, USA
* To whom correspondence should be addressed. E-mail: hlum{at}rush.edu.
Lysophosphatidylcholine (LPC) is a bioactive pro-inflammatory lipid which can be generated by pathological activities. We investigated the hypothesis that LPC signals increase of endothelial permeability. Stimulation of human dermal microvascular endothelial cells and bovine pulmonary microvascular endothelial cells with LPC (10 - 50 µM) induced decreases (within min) in transendothelial electrical resistance and increase of endothelial permeability. LPC activated (within 5 min) membrane-associated PKC phosphotransferase activity in the absence of translocation. Affinity-binding analysis indicated that LPC induced increases (also by 5 min) of GTP-bound RhoA, but not Rac1 nor Cdc42. By 60 min, both signaling pathways decreased towards baseline. Inhibition of RhoA with C3 transferase inhibited ~50% of LPC-induced resistance decrease. Pretreatment with PKC inhibitor GO6983 (concentrations selective for classic PKCs), PMA-induced depletion of PKC
, and transfection of antisense PKC oligonucleotide each prevented 40 - 50% of the LPC-induced resistance decrease. Furthermore, these three PKC inhibition strategies inhibited 60 - 80% of the LPC-induced GTP-bound RhoA. These results show that LPC directly impairs the endothelial barrier function that was dependent, at least in part, on cross-talk of PKC and RhoA signals. The evidence indicates that elevated LPC levels can contribute to the activation of a pro-inflammatory endothelial phenotype.
This article has been cited by other articles:
|
|
 |
|
  M. Guo, D. Daines, J. Tang, Q. Shen, R. M. Perrin, Y. Takada, S. Y. Yuan, and M. H. Wu Fibrinogen-{gamma} C-Terminal Fragments Induce Endothelial Barrier Dysfunction and Microvascular Leak via Integrin-Mediated and RhoA-Dependent Mechanism Arterioscler Thromb Vasc Biol, March 1, 2009; 29(3): 394 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Qiao, O. Holian, B.-S. Lee, F. Huang, J. Zhang, and H. Lum Phosphorylation of GTP dissociation inhibitor by PKA negatively regulates RhoA Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1161 - C1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Klinger, J. D. Murray, B. Casserly, D. F. Alvarez, J. A. King, S. S. An, G. Choudhary, A. N. Owusu-Sarfo, R. Warburton, and E. O. Harrington Rottlerin causes pulmonary edema in vivo: a possible role for PKC{delta} J Appl Physiol, December 1, 2007; 103(6): 2084 - 2094. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Ojala, T. E. Hirvonen, M. Hermansson, P. Somerharju, and J. Parkkinen Acyl chain-dependent effect of lysophosphatidylcholine on human neutrophils J. Leukoc. Biol., December 1, 2007; 82(6): 1501 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. White, P. Rastogi, and J. McHowat Lysoplasmenylcholine increases neutrophil adherence to human coronary artery endothelial cells Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1467 - C1471. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Qiao, F. Huang, R. P. Naikawadi, K. S. Kim, T. Said, and H. Lum Lysophosphatidylcholine impairs endothelial barrier function through the G protein-coupled receptor GPR4 Am J Physiol Lung Cell Mol Physiol, July 1, 2006; 291(1): L91 - L101. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pulinilkunnil and B. Rodrigues Cardiac lipoprotein lipase: Metabolic basis for diabetic heart disease Cardiovasc Res, February 1, 2006; 69(2): 329 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Mehta Lysophosphatidylcholine: an enigmatic lysolipid Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L174 - L175. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
