PMID- 17525826
OWN - NLM
STAT- MEDLINE
DCOM- 20071120
LR  - 20181201
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 302
IP  - 1-2
DP  - 2007 Aug
TI  - Homocysteine-induced biochemical stress predisposes to cytoskeletal remodeling in 
      stretched endothelial cells.
PG  - 133-43
AB  - Cellular cytoskeletal remodeling reflects alterations in local biochemical and 
      mechanical changes in terms of stress that manifests relocation of signaling 
      molecules within and across the cell. Although stretching due to load and 
      chemical changes by high homocysteine (HHcy) causes cytoskeletal re-arrangement, 
      the synergism between stretch and HHcy is unclear. We investigated the 
      contribution of HHcy in cyclic stretch-induced focal adhesion (FA) protein 
      redistribution leading to cytoskeletal re-arrangement in mouse aortic endothelial 
      cells (MAEC). MAEC were subjected to cyclic stretch (CS) and HHcy alone or in 
      combination. The redistribution of FA protein, and small GTPases were determined 
      by Confocal microscopy and Western blot techniques in membrane and cytosolic 
      compartments. We found that each treatment induces focal adhesion kinase (FAK) 
      phosphorylation and cytoskeletal actin polymerization. In addition, CS activates 
      and membrane translocates small GTPases RhoA with minimal effect on Rac1, whereas 
      HHcy alone is ineffective in both GTPases translocation. However, the combined 
      effect of CS and HHcy activates and membrane translocates both GTPases. Free 
      radical scavenger NAC (N-Acetyl-Cysteine) inhibits CS and HHcy-mediated FAK 
      phosphorylation and actin stress fiber formation. Interestingly, CS also 
      activates and membrane translocates another FA protein, paxillin in HHcy 
      condition. Cytochalasin D, an actin polymerization blocker and PI3-kinase 
      inhibitor Wortmannin inhibited FAK phosphorylation and membrane translocation of 
      paxillin suggesting the involvement of PI3K pathway. Together our results suggest 
      that CS- and HHcy-induced oxidative stress synergistically contribute to small 
      GTPase membrane translocation and focal adhesion protein redistribution leading 
      to endothelial remodeling.
FAU - Sen, Utpal
AU  - Sen U
AD  - Department of Physiology & Biophysics, HSC, University of Louisville School of 
      Medicine, A-1215, 500 South Preston Street, Louisville, KY 40202, USA.
FAU - Moshal, Karni S
AU  - Moshal KS
FAU - Singh, Mahavir
AU  - Singh M
FAU - Tyagi, Neetu
AU  - Tyagi N
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070525
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (Actins)
RN  - 0 (Androstadienes)
RN  - 0 (Paxillin)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 22144-77-0 (Cytochalasin D)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - Actins/metabolism
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Biomechanical Phenomena
MH  - Cells, Cultured
MH  - Cytochalasin D/pharmacology
MH  - Cytoskeleton/*drug effects/*metabolism
MH  - Endothelial Cells/*cytology/*drug effects/enzymology
MH  - Enzyme Activation/drug effects
MH  - Focal Adhesion Protein-Tyrosine Kinases/metabolism
MH  - Homocysteine/*pharmacology
MH  - Hyperhomocysteinemia/enzymology
MH  - Mice
MH  - Oxidative Stress/*drug effects
MH  - Paxillin/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Transport/drug effects
MH  - Wortmannin
MH  - rac GTP-Binding Proteins/metabolism
MH  - rhoA GTP-Binding Protein/metabolism
EDAT- 2007/05/26 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/05/26 09:00
PHST- 2006/12/12 00:00 [received]
PHST- 2007/02/09 00:00 [accepted]
PHST- 2007/05/26 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/05/26 09:00 [entrez]
AID - 10.1007/s11010-007-9435-4 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2007 Aug;302(1-2):133-43. doi: 10.1007/s11010-007-9435-4. Epub 
      2007 May 25.