scholarly journals DNA Methylation Inhibitor Regulates Guanylyl Cyclase/Natriuretic Peptide Receptor‐A Gene Expression in Mesangial Cells

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Prerna Kumar ◽  
Kailash Pandey
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Mesangial Cells ◽  
Natriuretic Peptide Receptor ◽  
Peptide Receptor ◽  
Methylation Inhibitor ◽  
Natriuretic Peptide Receptor A ◽  
Dna Methylation Inhibitor

scholarly journals Role of FQQI motif in the internalization, trafficking, and signaling of guanylyl-cyclase/natriuretic peptide receptor-A in cultured murine mesangial cells

2016 ◽  
Vol 310 (1) ◽  
pp. F68-F84 ◽  
Author(s):  
Indra Mani ◽  
Renu Garg ◽  
Kailash N. Pandey
Keyword(s):  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Mesangial Cells ◽  
Adaptor Protein ◽  
Target Cells ◽  
Natriuretic Peptide Receptor ◽  
Subcellular Trafficking ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A

Binding of the cardiac hormone atrial natriuretic peptide (ANP) to transmembrane guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA), produces the intracellular second messenger cGMP in target cells. To delineate the critical role of an endocytic signal in intracellular sorting of the receptor, we have identified a FQQI (Phe790, Gln791, Gln792, and Ile793) motif in the carboxyl-terminal region of NPRA. Mouse mesangial cells (MMCs) were transiently transfected with the enhanced green fluorescence protein (eGFP)-tagged wild-type (WT) and mutant constructs of eGFP-NPRA. The mutation FQQI/AAAA, in the eGFP-NPRA cDNA sequence, markedly attenuated the internalization of mutant receptors by almost 49% compared with the WT receptor. Interestingly, we show that the μ1B subunit of adaptor protein-1 binds directly to a phenylalanine-based FQQI motif in the cytoplasmic tail of the receptor. However, subcellular trafficking indicated that immunofluorescence colocalization of the mutated receptor with early endosome antigen-1 (EEA-1), lysosome-associated membrane protein-1 (LAMP-1), and Rab 11 marker was decreased by 57% in early endosomes, 48% in lysosomes, and 42% in recycling endosomes, respectively, compared with the WT receptor in MMCs. The receptor containing the mutated motif (FQQI/AAAA) also produced a significantly decreased level of intracellular cGMP during subcellular trafficking than the WT receptor. The coimmunoprecipitation assay confirmed a decreased level of colocalization of the mutant receptor with subcellular compartments during endocytic processes. The results suggest that the FQQI motif is essential for the internalization and subcellular trafficking of NPRA during the hormone signaling process in intact MMCs.

Angiotensin II Represses Guanylyl Cyclase/Natriuretic Peptide Receptor‐A Gene Expression and Receptor Signaling and Function

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Kiran K. Arise ◽  
Prerna Kumar ◽  
Ramachandran Samivel ◽  
Hanqing Zhao ◽  
Sarah Lindsey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Natriuretic Peptide Receptor ◽  
Receptor Signaling ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
And Function

Genetic disruption of guanylyl cyclase/natriuretic peptide receptor-A upregulates ACE and AT1 receptor gene expression and signaling: role in cardiac hypertrophy

2007 ◽  
Vol 31 (2) ◽  
pp. 193-202 ◽  
Author(s):  
Elangovan Vellaichamy ◽  
Di Zhao ◽  
Naveen Somanna ◽  
Kailash N. Pandey
Keyword(s):  
Gene Expression ◽  
Cardiac Hypertrophy ◽  
Natriuretic Peptide ◽  
Guanylyl Cyclase ◽  
Heart Weight ◽  
Natriuretic Peptide Receptor ◽  
Wild Type ◽  
Peptide Receptor ◽  
Natriuretic Peptide Receptor A ◽  
Npr1 Gene

Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) signaling antagonizes the physiological effects mediated by the renin-angiotensin system (RAS). The objective of this study was to determine whether the targeted-disruption of Npr1 gene (coding for GC-A/NPRA) leads to the activation of cardiac RAS genes involved on the hypertrophic remodeling process. The Npr1 gene-knockout ( Npr1 −/−) mice showed 30–35 mmHg higher systolic blood pressure (SBP) and a 63% greater heart weight-to-body weight (HW/BW) ratio compared with wild-type ( Npr1 +/+) mice. The mRNA levels of both angiotensin-converting enzyme and angiotensin II type 1a receptor were increased by three- and fourfold, respectively, in Npr1 −/− null mutant mice hearts compared with the wild-type Npr1 +/+ mice hearts. In parallel, the expression levels of interleukin-6 and tumor necrosis factor-α were increased by four- to fivefold, in Npr1 −/− mice hearts compared with control animals. The NF-κB binding activity in nuclear extracts of Npr1 −/− mice hearts was increased by fourfold compared with wild-type Npr1 +/+ mice hearts. Treatments with captopril or hydralazine equally attenuated SBP; however, only captopril significantly decreased the HW/BW ratio and suppressed cytokine gene expression in Npr1 −/− mice hearts. The ventricular cGMP level was reduced by almost sixfold in Npr1 −/− mice compared with wild-type control mice. The results of the present study indicate that disruption of NPRA/cGMP signaling leads to the augmented expression of cardiac RAS pathways that promote the development of cardiac hypertrophy and remodeling.

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