scholarly journals Angiotensin II induces upregulation of AT1 receptors via the sequential activation of transcription factors NFkB, Elk‐1 and AP‐1 in Cath.a cells

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Amit Kumar Mitra ◽  
Lie Gao ◽  
Irving H Zucker
Keyword(s):  
Transcription Factors ◽  
Angiotensin Ii ◽  
At1 Receptors ◽  
Activation Of Transcription ◽  
Sequential Activation ◽  
Cath.A Cells

scholarly journals Angiotensin II-induced upregulation of AT1 receptor expression: sequential activation of NF-κB and Elk-1 in neurons

2010 ◽  
Vol 299 (3) ◽  
pp. C561-C569 ◽  
Author(s):  
Amit K. Mitra ◽  
Lie Gao ◽  
Irving H. Zucker
Keyword(s):  
Transcription Factors ◽  
Angiotensin Ii ◽  
Time Course ◽  
Cell Model ◽  
Neuronal Cell ◽  
Nuclear Factor Κb ◽  
Receptor Expression ◽  
Ang Ii ◽  
Mobility Shift ◽  
Sequential Activation

It has been clearly established that increased circulating angiotensin II (ANG II) with concurrent upregulation of brain and peripheral ANG II type 1 receptors (AT1R) are important mediators in the pathophysiology of several diseases characterized by sympatho-excitation. In an effort to further understand the regulation of AT1R expression in neurons, we determined the role of sequential activation of the transcription factors nuclear factor-κB (NF-κB) and Ets-like protein 1 (Elk-1) in AT1R upregulation. We used CATH.a neurons as our neuronal cell model. Cells were treated with ANG II (100 nM) over a preset time course. Following ANG II activation, there was a temporal increase in the p65 subunit of NF-κB that was observed at 30 min, peaked at 1 h, and was sustained up to 24 h. There was a concomitant decrease of IκB and increased IκK expression. We also observed an increase in AT1R expression which followed the temporal increase of NF-κB. The activation of NF-κB was blocked by using the inhibitors parthenolide or p65 small interfering RNA (siRNA) which both led to a decrease in AT1R expression. The expression of Elk-1 was upregulated over a time period following ANG II activation and was decreased following NF-κB inhibition. p65-DNA binding was assessed using electrophoretic mobility shift assay, and it was shown that there was a time-dependent increased binding that was inhibited by means of parthenolide pretreatment or siRNA-mediated p65 gene silencing. Therefore, our results suggest a combined role for the transcription factors NF-κB and Elk-1 in the upregulation of AT1R in the CATH.a cell neuronal model. These data imply a positive feedback mechanism that may impact neuronal discharge sensitivity in response to ANG II.

Angiotensin II induces a complex activation of transcription factors in the rat brain: expression of Fos, Jun and Krox proteins

Neuroscience ◽  
1995 ◽  
Vol 65 (1) ◽  
pp. 93-99 ◽  
Author(s):  
C.J. Lebrun ◽  
A. Blume ◽  
T. Herdegen ◽  
K. Seifert ◽  
R. Bravo ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Angiotensin Ii ◽  
Rat Brain ◽  
Activation Of Transcription ◽  
Brain Expression

Benzo[a]pyrene-dependent activation of transcription factors NF-κB and AP-1 related to tumor promotion in hepatoma cell cultures

2007 ◽  
Vol 72 (5) ◽  
pp. 552-557 ◽  
Author(s):  
N. A. Bolotina ◽  
A. V. Gasparian ◽  
T. K. Dubovaja ◽  
V. A. Evteev ◽  
V. A. Kobliakov
Keyword(s):  
Transcription Factors ◽  
Cell Cultures ◽  
Hepatoma Cell ◽  
Tumor Promotion ◽  
Activation Of Transcription

scholarly journals Angiotensin II-Induced Protein Kinase D Activates the ATF/CREB Family of Transcription Factors and Promotes StAR mRNA Expression

Endocrinology ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 2524-2533 ◽  
Author(s):  
Lawrence O. Olala ◽  
Vivek Choudhary ◽  
Maribeth H. Johnson ◽  
Wendy B. Bollag
Keyword(s):  
Transcription Factors ◽  
Angiotensin Ii ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Dominant Negative ◽  
Protein Kinase D ◽  
Dependent Manner ◽  
Aldosterone Production ◽  
Glomerulosa Cells ◽  
Constitutively Active

Aldosterone synthesis is initiated upon the transport of cholesterol from the outer to the inner mitochondrial membrane, where the cholesterol is hydrolyzed to pregnenolone. This process is the rate-limiting step in acute aldosterone production and is mediated by the steroidogenic acute regulatory (StAR) protein. We have previously shown that angiotensin II (AngII) activation of the serine/threonine protein kinase D (PKD) promotes acute aldosterone production in bovine adrenal glomerulosa cells, but the mechanism remains unclear. Thus, the purpose of this study was to determine the downstream signaling effectors of AngII-stimulated PKD activity. Our results demonstrate that overexpression of the constitutively active serine-to-glutamate PKD mutant enhances, whereas the dominant-negative serine-to-alanine PKD mutant inhibits, AngII-induced StAR mRNA expression relative to the vector control. PKD has been shown to phosphorylate members of the activating transcription factor (ATF)/cAMP response element binding protein (CREB) family of leucine zipper transcription factors, which have been shown previously to bind the StAR proximal promoter and induce StAR mRNA expression. In primary glomerulosa cells, AngII induces ATF-2 and CREB phosphorylation in a time-dependent manner. Furthermore, overexpression of the constitutively active PKD mutant enhances the AngII-elicited phosphorylation of ATF-2 and CREB, and the dominant-negative mutant inhibits this response. Furthermore, the constitutively active PKD mutant increases the binding of phosphorylated CREB to the StAR promoter. Thus, these data provide insight into the previously reported role of PKD in AngII-induced acute aldosterone production, providing a mechanism by which PKD may be mediating steroidogenesis in primary bovine adrenal glomerulosa cells.

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