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Protein Kinase C Mediates the Angiotensin II‐Dependent Transcriptional Repression and Expression of Natriuretic Peptide Receptor‐A Gene
Author(s) -
Arise Kiran K,
Pandey Kailash N.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb70-a
Subject(s) - protein kinase c , npr1 , angiotensin ii , microbiology and biotechnology , atrial natriuretic peptide , transcriptional regulation , protein kinase a , npr2 , gene expression , biology , receptor , chemistry , signal transduction , endocrinology , medicine , kinase , gene , natriuretic peptide , biochemistry , heart failure
The objective of this study was to determine the transcriptional regulation of Npr 1 gene (coding for guanylyl cyclase/natriuretic peptide receptor‐A; NPRA) by the vasoactive hormone angiotensin II (Ang II). NPRA synthesizes the intracellular second messenger cGMP in response to ANP binding. The studies on the effect of Ang II on the promoter activity and expression of Npr 1 gene were carried out in cultured mouse mesangial cells. The cells were cultured in Dulbeccos modified Eagles medium (DMEM) containing 10% fetal bovine serum, and transiently transfected using Lipofectamine‐2000 reagent. Hormone treatments were carried out in serum‐free DMEM containing 0.1% bovine serum albumin. Promoter analysis of Npr 1 gene showed that the region approximately −1182 bp to −916 bp upstream of transcription start site contains cis ‐elements involved in Ang II‐mediated transcriptional repression. The data showed that Ang II‐mediated transcriptional repression of Npr 1 gene is mediated through AT 1 receptor subtype. The luciferase assay data from protein kinase inhibitors clearly suggested that the repression is mediated by both protein kinase C (PKC) and tyrosine kinase pathways. The PKC in particular has an additive effect on the Ang II mediated transcriptional repression and expression. The findings of this study will be critical in understanding the role of ANG‐II and PKC in the transcriptional regulation of Npr 1 gene and the pathophysiology of hypertension and homeostasis.