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Hyperglycemia Alters Angiotensin Type 1 Receptor Expression Through MAP‐Kinase Signaling Pathway in Liver Cells
Author(s) -
Thekkumkara Thomas,
Smith Jessica,
Thomas Jason,
Thangavel Samikkannu,
Gunaje Jayarama
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.a969-a
Subject(s) - downregulation and upregulation , angiotensin ii receptor type 1 , signal transduction , angiotensin ii , kinase , endocrinology , mapk/erk pathway , medicine , receptor , microbiology and biotechnology , chemistry , mitogen activated protein kinase , biology , biochemistry , gene
Overwhelming evidence indicates a role for angiotensin type 1 receptor (AT1) in the progression of diabetic complications. Therefore much effort has been directed towards identifying the receptor role in diabetes, and very little attention is given to the role of hyperglycemia on receptor expression. Recently, we have shown that high glucose (25 mM) downregulates AT1 gene transcription in human proximal tubule cells. In this study we used WB, a continuously passaged rat liver epithelial cell line, which expresses the native AT1. Cells were exposed to normal glucose (5.5 mM) and high glucose (25 mM), and hyperglycemia‐mediated changes in receptor expression and signaling intermediates were determined. Exposure of cells to high glucose resulted in downregulation of AT1 cell surface binding at 48 h. without a change in the affinity of the receptor. Consistent with the receptor downregulation we observed glucose‐induced downregulation of AT1 mRNA. Under similar conditions, there was an increase in the phosphorylation of PKC epsilon and extracellular signal regulated kinase (ERK) or MAP kinases p42 & p44. Pretreatment of cells with MAP kinase specific inhibitor (PD 98059) reversed glucose induced AT1 downregulation. These studies demonstrate for the first time increase in extracellular glucose inhibits AT1 gene expression through MAP kinase(s) signaling pathways. Supported by NIH Grant HL61356