Mercuric Ion Attenuates Nuclear Factor-κB Activation and DNA Binding in Normal Rat Kidney Epithelial Cells: Implications for Mercury-Induced Nephrotoxicity

2001 ◽  
Vol 173 (3) ◽  
pp. 176-187 ◽  
Author(s):  
Francisco J. Dieguez-Acuña ◽  
Maureen E. Ellis ◽  
John Kushleika ◽  
James S. Woods
Keyword(s):  
Dna Binding ◽  
Epithelial Cells ◽  
Rat Kidney ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Mercuric Ion ◽  
Normal Rat ◽  
Kidney Epithelial Cells

scholarly journals DNA microarray analysis of normal rat kidney epithelial cells treated with cadmium

2011 ◽  
Vol 36 (1) ◽  
pp. 127-129 ◽  
Author(s):  
Maki Tokumoto ◽  
Tomoaki Ohtsu ◽  
Akiko Honda ◽  
Yasuyuki Fujiwara ◽  
Hisamitsu Nagase ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Microarray Analysis ◽  
Dna Microarray ◽  
Rat Kidney ◽  
Dna Microarray Analysis ◽  
Normal Rat ◽  
Kidney Epithelial Cells

Effects of testosterone and 17, β– estradiol on the polyamine metabolism in cultivated normal rat kidney epithelial cells

Amino Acids ◽  
2000 ◽  
Vol 18 (4) ◽  
pp. 353-361 ◽  
Author(s):  
I. Jotova ◽  
C. Wang ◽  
A. Tabib ◽  
O. Dimitrov ◽  
U. Bachrach
Keyword(s):  
Epithelial Cells ◽  
Rat Kidney ◽  
Polyamine Metabolism ◽  
Normal Rat ◽  
Kidney Epithelial Cells

scholarly journals Intracellular Na+ directly modulates Na+,K+-ATPase gene expression in normal rat kidney epithelial cells

2000 ◽  
Vol 57 (4) ◽  
pp. 1617-1635 ◽  
Author(s):  
Shigeaki Muto ◽  
Jun Nemoto ◽  
Koji Okada ◽  
Yukio Miyata ◽  
Kiyoshi Kawakami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Rat Kidney ◽  
Atpase Gene ◽  
Normal Rat ◽  
Kidney Epithelial Cells

RhoA regulation of NF-κB activation is mediated by COX-2-dependent feedback inhibition of IKK in kidney epithelial cells

2007 ◽  
Vol 293 (3) ◽  
pp. C1160-C1170 ◽  
Author(s):  
William W. Polk ◽  
Maureen E. Ellis ◽  
John V. Kushleika ◽  
P. Lynne Simmonds ◽  
James S. Woods
Keyword(s):  
Dna Binding ◽  
Epithelial Cells ◽  
Feedback Inhibition ◽  
Rat Kidney ◽  
Constitutive Expression ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Cox 2 ◽  
Kidney Epithelial Cells ◽  
Iκbα Phosphorylation

Numerous studies have demonstrated a central role of renal tubular epithelial cells in the etiology of kidney injury and disease through the elaboration of inflammatory mediators. However, little is known about the cellular signaling mechanisms involved in this process. In this study we employed normal rat kidney epithelial (NRK52E) cells to identify a novel LPS-induced signaling pathway in which RhoA-mediated AP-1 activity promotes expression of cyclooxygenase-2 (COX-2) with consequent feedback inhibition of NF-κB activation through IKKβ. Inhibition of RhoA signaling using either the RhoA kinase inhibitor Y-27632 or a dominant negative mutant of RhoA (RhoA-DN) dramatically extended the duration of p65-DNA binding, IκBα phosphorylation, and IKKβ activity following LPS treatment. Prolongation of events associated with NF-κB activation was also observed in cells pretreated and/or cotransfected with the JNK inhibitor SP600125 or deletion mutants of MEKK1 (MEKK1-KD) or Jun (Jun-DN). Conversely, constitutive expression of RhoA prevented NF-κB activation by LPS, and this effect was reversed by cotransfection with MEKK1-KD. In addition, we found that the RhoA/AP-1 signaling axis plays a necessary role in COX-2 expression by LPS and that this effect is independent of NF-κB activation. Moreover, inhibition of COX-2 activity results in persistent p65-DNA binding, IκBα phosphorylation, and IKKβ activity, similar to that observed after prevention of RhoA/AP-1 axis signaling. These findings suggest that COX-2 links the RhoA/AP-1 signaling cascade to NF-κB activation, thereby defining a novel integrated model for regulation of the inflammatory response of kidney epithelial cells to LPS and potentially other external stimuli.

A direct requirement of nuclear factor-κB for suppression of apoptosis in ventricular myocytes

2000 ◽  
Vol 279 (3) ◽  
pp. H939-H945 ◽  
Author(s):  
Shareef Mustapha ◽  
Alla Kirshner ◽  
Danielle De Moissac ◽  
Lorrie A. Kirshenbaum
Keyword(s):  
Dna Binding ◽  
Gene Transcription ◽  
Ventricular Myocytes ◽  
Vital Staining ◽  
Fold Increase ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Cytoplasmic Factor ◽  
Tnf Α ◽  
Factor Α

Nuclear factor-κB (NF-κB) is a ubiquitously expressed cellular factor regulated by the cytoplasmic factor inhibitor protein κBα (IκBα). Activation of NF-κB by cytokines, including tumor necrosis factor-α (TNF-α), requires the phosphorylation and degradation of IκBα. An anti-apoptotic role for NF-κB has recently been suggested. In the present study, we ascertained whether death-promoting signals and apoptosis mediated by TNF-α are suppressed by NF-κB in postnatal ventricular myocytes. Stimulation of myocytes with TNF-α resulted in a 12.1-fold increase ( P < 0.01) in NF-κB-dependent gene transcription and DNA binding compared with controls. This was accompanied by a corresponding increase in the NF-κB target protein A20 as determined by Western blot analysis. Vital staining revealed that TNF-α was not cytotoxic to myocytes and did not provoke apoptosis. Adenovirus-mediated delivery of a nonphosphorylatable form of IκBα to inactivate NF-κB prevented TNF-α-stimulated NF-κB-dependent gene transcription and nuclear NF-κB DNA binding. Importantly, myocytes stimulated with TNF-α and defective for NF-κB activation resulted in a 2.2-fold increase ( P < 0.001) in apoptosis. To our knowledge, the data provide the first indication that a functional NF-κB signaling pathway is crucial for suppressing death-promoting signals mediated by TNF-α in ventricular myocytes.

scholarly journals Immunoglobulin light chains activate nuclear factor-κB in renal epithelial cells through a Src-dependent mechanism

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1301-1307 ◽  
Author(s):  
Wei-Zhong Ying ◽  
Pei-Xuan Wang ◽  
Kristal J. Aaron ◽  
Kolitha Basnayake ◽  
Paul W. Sanders
Keyword(s):  
Epithelial Cells ◽  
Tyrosine Phosphorylation ◽  
Renal Injury ◽  
Src Kinase ◽  
Nuclear Factor Κb ◽  
Light Chains ◽  
Nuclear Factor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Renal Epithelial Cells ◽  
Iκb Kinase

Abstract One of the major attendant complications of multiple myeloma is renal injury, which contributes significantly to morbidity and mortality in this disease. Monoclonal immunoglobulin free light chains (FLCs) are usually directly involved, and tubulointerstitial renal injury and fibrosis are prominent histologic features observed in myeloma. The present study examined the role of monoclonal FLCs in altering the nuclear factor κ light chain enhancer of activated B cells (NF-κB) activity of renal epithelial cells. Human proximal tubule epithelial cells exposed to 3 different human monoclonal FLCs demonstrated Src kinase–dependent activation of the NF-κB pathway, which increased production of monocyte chemoattractant protein-1 (MCP-1). Tyrosine phosphorylation of inhibitor of κB kinases (IKKs) IKKα and IKKβ and a concomitant increase in inhibitor of κB (IκB) kinase activity in cell lysates were observed. Time-dependent, Src kinase–dependent increases in serine and tyrosine phosphorylation of IκBα and NF-κB activity were also demonstrated. Proteasome inhibition partially blocked FLC-induced MCP-1 production. These findings fit into a paradigm characterized by FLC-induced redox-signaling events that activated the canonical and atypical (IKK-independent) NF-κB pathways to promote a proinflammatory, profibrotic renal environment.

UV stimulation induces nuclear factor κB (NF-κB) DNA-binding activity but not transcriptional activation

2001 ◽  
Vol 29 (6) ◽  
pp. 688-691 ◽  
Author(s):  
K. J. Campbell ◽  
N. R. Chapman ◽  
N. D. Perkins
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Cellular Response ◽  
Uv Light ◽  
Binding Protein ◽  
Nuclear Factor Κb ◽  
Camp Response Element Binding ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Dna Binding Activity

The cellular response to DNA-damaging agents is partly mediated by DNA-binding transcription factors such as p53 and nuclear factor κB (NF-κB). Typically NF-κB activation is associated with resistance to apoptosis. Following stimulation with UV light however, NF-κB activation has been shown to be required for programmed cell death. To study this effect further and to determine the relationship between NF-κB and p53 function, we have examined the effect of UV light on U2OS cells. UV stimulation resulted in the activation of NF-κB DNA-binding and the induction of p53. Surprisingly, and in contrast with tumour necrosis factor α stimulation, this UV-induced NF-κB was transcriptionally inert. These observations suggest a model in which the NF-κB switch from an anti-apoptotic to a pro-apoptotic role within the cell results from modulation of its ability to stimulate gene expression, possibly as a result of the ability of p53 to sequester transcriptional co-activator proteins such as p300/CREB (cAMP-response-element-binding protein)-binding protein.

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