Inducible nitric oxide synthase-dependent stimulation of PKGI and phosphorylation of VASP in human embryonic kidney cells

André, Muriel; Latado, Hélia; Felley‐Bosco, Emanuela

doi:10.1016/j.bcp.2004.11.007

Cited by 16 publications

(15 citation statements)

References 53 publications

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“…In addition, NO has been shown to regulate VASP (29). In response to physiologic concentrations of NO, VASP immunolocalization was altered, VASP protein expression was increased, VASP was concentrated in the filopodia, and VASP phosphorylation was markedly increased.…”

Section: Discussionmentioning

confidence: 92%

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Nitric Oxide Cytoskeletal-Induced Alterations Reverse the Endothelial Progenitor Cell Migratory Defect Associated With Diabetes

Segal¹

2006

Diabetes

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Stromal-derived factor-1 (SDF-1) is a critical chemokine for endothelial progenitor cell (EPC) recruitment to areas of ischemia, allowing these cells to participate in compensatory angiogenesis. The SDF-1 receptor, CXCR4, is expressed in developing blood vessels as well as on CD34؉ EPCs. We describe that picomolar and nanomolar concentrations of SDF-1 differentially influence neovascularization, inducing CD34؉ cell migration and EPC tube formation. CD34؉ cells isolated from diabetic patients demonstrate a marked defect in migration to SDF-1. This defect is associated, in some but not all patients, with a cell surface activity of CD26/dipeptidyl peptidase IV, an enzyme that inactivates SDF-1. Diabetic CD34؉ cells also do not migrate in response to vascular endothelial growth factor and are structurally rigid. However, incubating CD34؉ cells with a nitric oxide (NO) donor corrects this migration defect and corrects the cell deformability. In addition, exogenous NO alters vasodilator-stimulated phosphoprotein and mammalian-enabled distribution in EPCs. These data support a common downstream cytoskeletal alteration in diabetic CD34؉ cells that is independent of growth factor receptor activation and is correctable with exogenous NO. This inability of diabetic EPCs to respond to SDF-1 may contribute to aberrant tissue vascularization and endothelial repair in diabetic patients. Diabetes 55: 102-109, 2006

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Section: Discussionmentioning

confidence: 92%

“…This family of proteins is critical to actin elongation, powering the expansile apparatuses of cells, the filopodia and lamellapodia, (27 and recently rev. in 28) and is regulated by NO (29). Immunohistochemistry of VASP protein was performed on cultured EPCs.…”

Section: Cd34؉ Cells and Microvascular Endothelial Cells Re-mentioning

confidence: 99%

Nitric Oxide Cytoskeletal-Induced Alterations Reverse the Endothelial Progenitor Cell Migratory Defect Associated With Diabetes

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2006

Diabetes

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“…Western blots to detect iNOS protein were carried out as previously described using NO53 antibody (Felley-Bosco et al, 2000;Andre et al, 2005;Rumbo et al, 2005). To determine tyrosine phosphorylation membranes were incubated overnight with 2% gelatin (Sigma, Buchs, Switzerland) in PBS-T (PBS (pH 7.4), 0.1% Tween-20), blots were incubated with mouse monoclonal anti-phosphotyrosine antibodies (1:2500) (PY20, Transduction Laboratories, San Diego, CA, USA).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Human intestinal epithelial DLD-1 and HEK 293 cells were cultured as described previously (Felley-Bosco et al, 2000;Andre et al, 2005). In some experiments, DLD-1 cells stimulated for 14 h by cytokines (Felley-Bosco et al, 2000) were exposed to PV prepared according to Huyer et al (1997).…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

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Src-mediated phosphorylation regulates subcellular distribution and activity of human inducible nitric oxide synthase

et al. 2005

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Inducible nitric oxide synthase (iNOS) expression is regulated at both the transcriptional and post-transcriptional level in epithelial cells. The aim of this study was to characterize the effects of tyrosine phosphorylation on iNOS activity. In a human intestinal epithelial cell line stimulated with cytokines, tyrosine phosphorylation of human iNOS protein was observed after 30 min exposure to pervanadate (PV), an inhibitor of protein tyrosine phosphatases. 4-Amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo [3,4-d]pyrimidine, a specific inhibitor of Src tyrosine kinases, abolished the PVinduced iNOS tyrosine phosphorylation. Cotransfection of Src with iNOS cDNA in human embryonic kidney (HEK) 293 cells resulted in a threefold (Po0.001) increase of iNOS protein levels and tyrosine phosphorylation of iNOS. In the presence of Src, 76% of wild-type (wt) iNOS was redistributed to detergent-insoluble domains and iNOS activity was decreased by 28% (Po0.05) despite increased iNOS protein levels. Analysis of iNOS tyrosine mutants revealed decreased Src-induced effects in Y151F iNOS mutant. Using a GST-fusion protein containing a domain encompassing Y151, we show that Y151 is a direct substrate for active Src in vitro. These findings indicate a role for iNOS tyrosine phosphorylation in the regulation of iNOS activity and the implication of Src tyrosine kinases in this pathway.

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Comparative effects of selective and non-selective nitric oxide synthase inhibition in gentamicin-induced rat nephrotoxicity

Ghaznavi

Kadkhodaee

2006

Arch Toxicol

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Different nitric oxide synthase (NOS) isoforms are found in the kidney. Some studies provided evidences that increased endothelial NOS (eNOS) activity leads to restoration of renal function after injury, but activation of inducible NOS (iNOS) aggravates renal failure. In the present study, the beneficial effects of selective iNOS blockade in gentamicin (GM) induced nephrotoxicity have been investigated. Four groups of rats were studied. Untreated control rats received saline. In GM group, GM was injected (IV, 4 mg kg(-1)). In GM + L-NAME group rats received L-NAME (N-omega-L-arginine methyl ester, a non-selective NOS inhibitor) simultaneously with GM (IV, 30 mg kg(-1)). Additional doses of L-NAME were administered 2 and 4 h after GM (IP, 30 mg kg(-1)). In GM + L-NIL group rats were treated by N-imino-ethyl lysine (L-NIL, a selective iNOS inhibitor). First dose (IV, 3 mg kg(-1)) administrated simultaneously with GM. Next doses (IP, 3 mg kg(-1)) were administered 2 and 4 h after GM. In all groups, serum and urine creatinine levels were measured. Creatinine clearance was calculated and considered as an estimation of glomerular filtration rate (GFR). Urine N-acetyl-b-D-glucose aminidase (NAG) activities were also determined. After experiments, kidney sections were histologically studied. Selective iNOS inhibition by L-NIL prevented the GM-induced decrease in GFR and increase in creatinine levels, while complete non-selective NOS inhibition by L-NAME aggravated the GFR reduction, elevation of creatinine levels and enzyme release (P < 0.05). Histological studies showed that GM-treated kidneys had evidences of tubular damages and these damages were less evident by the administration of L-NIL. In conclusion, selective inhibition of iNOS may prevent GM-induced nephrotoxicity, whereas non-selective inhibition of NOS aggravates it.

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Inducible nitric oxide synthase-dependent stimulation of PKGI and phosphorylation of VASP in human embryonic kidney cells

Cited by 16 publications

References 53 publications

Nitric Oxide Cytoskeletal-Induced Alterations Reverse the Endothelial Progenitor Cell Migratory Defect Associated With Diabetes

Nitric Oxide Cytoskeletal-Induced Alterations Reverse the Endothelial Progenitor Cell Migratory Defect Associated With Diabetes

Src-mediated phosphorylation regulates subcellular distribution and activity of human inducible nitric oxide synthase

Comparative effects of selective and non-selective nitric oxide synthase inhibition in gentamicin-induced rat nephrotoxicity

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