PortalPublikationenTumor necrosis factor-α-mediated suppression of dual-specifi...

Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival

Standard

Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival. / Kao, Derrick D; Oldebeken, Scott R; Rai, Anjali; Lubos, Edith; Leopold, Jane A; Loscalzo, Joseph; Handy, Diane E.

in: MOL CELL BIOCHEM, Jahrgang 382, Nr. 1-2, 10.2013, S. 153-162.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kao, DD, Oldebeken, SR, Rai, A, Lubos, E, Leopold, JA, Loscalzo, J & Handy, DE 2013, 'Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival', MOL CELL BIOCHEM, Jg. 382, Nr. 1-2, S. 153-162. https://doi.org/10.1007/s11010-013-1730-7

APA

Kao, D. D., Oldebeken, S. R., Rai, A., Lubos, E., Leopold, J. A., Loscalzo, J., & Handy, D. E. (2013). Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival. MOL CELL BIOCHEM, 382(1-2), 153-162. https://doi.org/10.1007/s11010-013-1730-7

Vancouver

Kao DD, Oldebeken SR, Rai A, Lubos E, Leopold JA, Loscalzo J et al. Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival. MOL CELL BIOCHEM. 2013 Okt;382(1-2):153-162. https://doi.org/10.1007/s11010-013-1730-7

Bibtex

@article{61aaab9cf0074289b3e063c04a73d689,
title = "Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival",
abstract = "We investigated the effects of tumor necrosis factor-α (TNF-α) exposure on mitogen-activated protein kinase signaling in human microvascular endothelial cells. TNF-α caused a significant suppression of a dual specificity phosphatase, DUSP4, that regulates ERK1/2 activation. Thus, we hypothesized that suppression of DUSP4 enhances cell survival by increasing ERK1/2 signaling in response to growth factor stimulation. In support of this concept, TNF-α pre-exposure increased growth factor-mediated ERK1/2 activation, whereas overexpression of DUSP4 with an adenovirus decreased ERK1/2 compared to an empty adenovirus control. Overexpression of DUSP4 also significantly decreased cell viability, lessened recovery in an in vitro wound healing assay, and decreased DNA synthesis. Pharmacological inhibition of NFκB activation or a dominant negative construct of the inhibitor of κB significantly lessened TNF-α-mediated suppression of DUSP4 expression by 70-84% and attenuated ERK activation, implicating NFκB-dependent pathways in the TNF-α-mediated suppression of DUSP4 that contributes to ERK1/2 signaling. Taken together, our findings show that DUSP4 attenuates ERK signaling and reduces cell viability, suggesting that the novel crosstalk between NFκB and MAPK pathways contributes to cell survival.",
keywords = "Cell Proliferation/drug effects, Cell Survival/drug effects, Dual-Specificity Phosphatases/antagonists & inhibitors, Endothelial Cells/cytology, Extracellular Signal-Regulated MAP Kinases/metabolism, Humans, Intercellular Signaling Peptides and Proteins/metabolism, Microvessels/cytology, Mitogen-Activated Protein Kinase Phosphatases/antagonists & inhibitors, NF-kappa B/metabolism, Signal Transduction/drug effects, Tumor Necrosis Factor-alpha/pharmacology",
author = "Kao, {Derrick D} and Oldebeken, {Scott R} and Anjali Rai and Edith Lubos and Leopold, {Jane A} and Joseph Loscalzo and Handy, {Diane E}",
year = "2013",
month = oct,
doi = "10.1007/s11010-013-1730-7",
language = "English",
volume = "382",
pages = "153--162",
journal = "MOL CELL BIOCHEM",
issn = "0300-8177",
publisher = "Springer Netherlands",
number = "1-2",

}

RIS

TY - JOUR

T1 - Tumor necrosis factor-α-mediated suppression of dual-specificity phosphatase 4: crosstalk between NFκB and MAPK regulates endothelial cell survival

AU - Kao, Derrick D

AU - Oldebeken, Scott R

AU - Rai, Anjali

AU - Lubos, Edith

AU - Leopold, Jane A

AU - Loscalzo, Joseph

AU - Handy, Diane E

PY - 2013/10

Y1 - 2013/10

N2 - We investigated the effects of tumor necrosis factor-α (TNF-α) exposure on mitogen-activated protein kinase signaling in human microvascular endothelial cells. TNF-α caused a significant suppression of a dual specificity phosphatase, DUSP4, that regulates ERK1/2 activation. Thus, we hypothesized that suppression of DUSP4 enhances cell survival by increasing ERK1/2 signaling in response to growth factor stimulation. In support of this concept, TNF-α pre-exposure increased growth factor-mediated ERK1/2 activation, whereas overexpression of DUSP4 with an adenovirus decreased ERK1/2 compared to an empty adenovirus control. Overexpression of DUSP4 also significantly decreased cell viability, lessened recovery in an in vitro wound healing assay, and decreased DNA synthesis. Pharmacological inhibition of NFκB activation or a dominant negative construct of the inhibitor of κB significantly lessened TNF-α-mediated suppression of DUSP4 expression by 70-84% and attenuated ERK activation, implicating NFκB-dependent pathways in the TNF-α-mediated suppression of DUSP4 that contributes to ERK1/2 signaling. Taken together, our findings show that DUSP4 attenuates ERK signaling and reduces cell viability, suggesting that the novel crosstalk between NFκB and MAPK pathways contributes to cell survival.

AB - We investigated the effects of tumor necrosis factor-α (TNF-α) exposure on mitogen-activated protein kinase signaling in human microvascular endothelial cells. TNF-α caused a significant suppression of a dual specificity phosphatase, DUSP4, that regulates ERK1/2 activation. Thus, we hypothesized that suppression of DUSP4 enhances cell survival by increasing ERK1/2 signaling in response to growth factor stimulation. In support of this concept, TNF-α pre-exposure increased growth factor-mediated ERK1/2 activation, whereas overexpression of DUSP4 with an adenovirus decreased ERK1/2 compared to an empty adenovirus control. Overexpression of DUSP4 also significantly decreased cell viability, lessened recovery in an in vitro wound healing assay, and decreased DNA synthesis. Pharmacological inhibition of NFκB activation or a dominant negative construct of the inhibitor of κB significantly lessened TNF-α-mediated suppression of DUSP4 expression by 70-84% and attenuated ERK activation, implicating NFκB-dependent pathways in the TNF-α-mediated suppression of DUSP4 that contributes to ERK1/2 signaling. Taken together, our findings show that DUSP4 attenuates ERK signaling and reduces cell viability, suggesting that the novel crosstalk between NFκB and MAPK pathways contributes to cell survival.

KW - Cell Proliferation/drug effects

KW - Cell Survival/drug effects

KW - Dual-Specificity Phosphatases/antagonists & inhibitors

KW - Endothelial Cells/cytology

KW - Extracellular Signal-Regulated MAP Kinases/metabolism

KW - Humans

KW - Intercellular Signaling Peptides and Proteins/metabolism

KW - Microvessels/cytology

KW - Mitogen-Activated Protein Kinase Phosphatases/antagonists & inhibitors

KW - NF-kappa B/metabolism

KW - Signal Transduction/drug effects

KW - Tumor Necrosis Factor-alpha/pharmacology

U2 - 10.1007/s11010-013-1730-7

DO - 10.1007/s11010-013-1730-7

M3 - SCORING: Journal article

C2 - 23812841

VL - 382

SP - 153

EP - 162

JO - MOL CELL BIOCHEM

JF - MOL CELL BIOCHEM

SN - 0300-8177

IS - 1-2

ER -