Comparison of the signaling mechanisms by which VEGF, H2O2, and phosphatase inhibitors activate endothelial cell ERK1/2 MAP-kinase

Tao, Qi; Spring, Simone C.; Terman, Bruce I.

doi:10.1016/j.mvr.2004.11.003

Cited by 18 publications

(28 citation statements)

References 29 publications

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“…Activation of PTK signaling by oxidative stress has been demonstrated in human smooth muscle cells and in gerbil hippocampus (Du et al 1999;Whisler et al 1994;Zalewska et al 2003). Others and we have shown that increase in PTK activity was accompanied by inactivation of PTP after ROS exposure in different cell types, including BMVEC (Chen et al 2006;Haorah J 2007b;Tao et al 2005). This concurrent event was due to transient oxidation of catalytic cysteine on PTP and trans-activation of PTK due to an autophosphorylation of PTK receptor in a reversible manner (Meng et al 2002).…”

Section: Discussionmentioning

confidence: 81%

Activation of protein tyrosine kinases and matrix metalloproteinases causes blood‐brain barrier injury: Novel mechanism for neurodegeneration associated with alcohol abuse

Haorah

Schall

Ramirez

et al. 2007

Glia

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Blood-brain barrier (BBB) formed by brain microvascular endothelial cells (BMVEC) regulates the passage of molecules and leukocytes in and out of the brain. Activation of matrix metalloproteinases (MMPs) and alteration of basement membrane (BM) associated with BBB injury were documented in stroke patients. While chronic alcoholism is a risk factor for developing stroke, underlying mechanisms are not well understood. We hypothesized that ethanol (EtOH)-induced protein tyrosine kinase (PTK) signaling resulted a loss of BBB integrity via MMPs activation and degradation of BM component, collagen IV. Treatment of BMVEC with EtOH or acetaldehyde (AA) for 2-48 hr increased MMP-1, -2 and -9 activities or decreased the levels of tissue inhibitors of MMPs (TIMP-1, -2) in a PTK-dependent manner without affecting protein tyrosine phosphatase activity. Enhanced PTK activity after EtOH exposure correlated with increased phosphorylated proteins of selective receptor and non-receptor PTKs. Up-regulation of MMPs activities and protein contents paralleled a decrease in collagen IV content, and inhibitors of EtOH metabolism, MMP-2 and 9, or PTK reversed all these effects. Using human BMVEC assembled into BBB models, we found that EtOH/AA diminished barrier tightness, augmented permeability, and monocyte migration across the BBB via activation of PTKs and MMPs. These findings suggest that alcohol associated BBB injury could be mediated by MMPs via BM protein degradation and could serve as a co-morbidity factor for neurological disorders like stroke or neuroinflammation. Furthermore, our preliminary experiments indicated that human astrocytes secreted high levels of MMP-1 and 9 following exposure to EtOH, suggesting the role of BM protein degradation and BBB compromise as a result of glial activation by ethanol. These results provide better understanding of multifaceted effects of alcohol on the brain and could help develop new therapeutic interventions. KeywordsBlood-brain barrier; brain endothelial cell; ethanol metabolism; matrix metalloproteinases; protein tyrosine kinase; protein tyrosine phosphatase

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Section: Discussionmentioning

confidence: 81%

Activation of protein tyrosine kinases and matrix metalloproteinases causes blood‐brain barrier injury: Novel mechanism for neurodegeneration associated with alcohol abuse

Haorah

Schall

Ramirez

et al. 2007

Glia

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“…ROS have been shown to influence c-Src at several levels, both directly by acting on c-Src to modulate its kinase activity (1,69,104) and indirectly by modulating factors that regulate c-Src kinase activity (11,30,86,106). Similarly, c-Src kinase activity appears to influence NADPH oxidasedependent ROS generation at several levels, by facilitating the activation of NADPH oxidase co-factors (Rac and p47phox) required for complex activation (19,36,110).…”

Section: Redoxosomal Signaling Via C-src In the Absence Of A Ligand Fmentioning

confidence: 99%

“…The exact mechanism(s) that underlies c-Src activation on redoxosomes remains to be clearly defined, but may involved both direct redox-activation of c-Src and the inactivation of protein tyrosine phosphatases that keep c-Src in an inactive dephosphorylated state (86,106). It is hypothesized that ROS can directly activate c-Src by modifying specific cysteine residues that activate the c-Src kinase domain (86).…”

mentioning

confidence: 99%

Signaling Components of Redox Active Endosomes: The Redoxosomes

Oakley

Abbott

et al. 2009

Antioxidants & Redox Signaling

180

160

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Subcellular compartmentalization of reactive oxygen species (ROS) plays a critical role in transmitting cell signals in response to environmental stimuli. In this regard, signals at the plasma membrane have been shown to trigger NADPH oxidase-dependent ROS production within the endosomal compartment and this step can be required for redox-dependent signal transduction. Unique features of redox-active signaling endosomes can include NADPH oxidase complex components (Nox1, Noxo1, Noxa1, Nox2, p47phox, p67phox, and=or Rac1), ROS processing enzymes (SOD1 and=or peroxiredoxins), chloride channels capable of mediating superoxide transport and=or membrane gradients required for Nox activity, and novel redox-dependent sensors that control Nox activity. This review will discuss the cytokine and growth factor receptors that likely mediate signaling through redox-active endosomes, and the common mechanisms whereby they act. Additionally, the review will cover ligand-independent environmental injuries, such as hypoxia=reoxygenation injury, that also appear to facilitate cell signaling through NADPH oxidase at the level of the endosome. We suggest that redox-active endosomes encompass a subset of signaling endosomes that we have termed redoxosomes. Redoxosomes are uniquely equipped with redox-processing proteins capable of transmitting ROS signals from the endosome interior to redox-sensitive effectors on the endosomal surface. In this manner, redoxosomes can control redoxdependent effector functions through the spatial and temporal regulation of ROS as second messengers. Antioxid. Redox Signal. 11, 1313-1333

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“…Treatment with pervanadate inhibits intracellular tyrosine phosphatases resulting in sustained phosphorylation of various tyrosine kinases and substrates reflecting the activation state of the cells (32). Tyrosine kinases so activated subsequently phosphorylate their substrates including certain downstream serine/threonine kinases resulting in their activa-tion (33).…”

Section: Phosphorylation Of T-cell Signaling Proteins In Jurkatmentioning

confidence: 99%

“…1, A and B). However, as mentioned under "Results," pervanadate treatment of cells leads to general phosphorylation of most of the intracellular tyrosine kinases and their substrates and is therefore not specific to a given pathway (32,33). Targeted stimulation of the T-cell activation pathway was achieved by anti-CD3 antibody as described below.…”

Section: Multiplex Suspension Array Analysis Of B-cell Signaling In Cmentioning

confidence: 99%

Multiplex Analysis of Intracellular Signaling Pathways in Lymphoid Cells by Microbead Suspension Arrays

Khan

Mendoza

Rhyne³

et al. 2006

Molecular & Cellular Proteomics

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Comparison of the signaling mechanisms by which VEGF, H2O2, and phosphatase inhibitors activate endothelial cell ERK1/2 MAP-kinase

Cited by 18 publications

References 29 publications

Activation of protein tyrosine kinases and matrix metalloproteinases causes blood‐brain barrier injury: Novel mechanism for neurodegeneration associated with alcohol abuse

Activation of protein tyrosine kinases and matrix metalloproteinases causes blood‐brain barrier injury: Novel mechanism for neurodegeneration associated with alcohol abuse

Signaling Components of Redox Active Endosomes: The Redoxosomes

Multiplex Analysis of Intracellular Signaling Pathways in Lymphoid Cells by Microbead Suspension Arrays

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