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Regulation of Renin Gene Expression by Oxidative Stress
Author(s) -
Itani Hana A,
Liu Xuebo,
Sigmund Curt D
Publication year - 2008
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.22.1_supplement.1160.6
Subject(s) - oxidative stress , gene expression , angiotensin ii , transcriptional regulation , transfection , microbiology and biotechnology , xanthine oxidase , endogeny , chemistry , regulation of gene expression , transcription (linguistics) , messenger rna , gene , endocrinology , biology , receptor , biochemistry , enzyme , linguistics , philosophy
Angiotensin‐II (AII) is involved in the pathogenesis of hypertension and mediates its effects in part by causing oxidative stress. AII feedback inhibits renin (REN) gene expression. To examine the effect of ROS on REN expression, we measured endogenous REN mRNA levels by RNase Protection in REN‐expressing As4.1 cells in response to increasing doses of hydrogen peroxide (HP). HP caused a dose dependent decrease in steady state REN mRNA levels. The effect of HP was most pronounced after 24hrs of treatment. ROS generated by xanthine and xanthine oxidase also significantly decreased REN mRNA. Blocking of transcription revealed that HP effect is transcriptionally mediated yet a post‐transcriptional component may be involved. To measure HP effect on REN promoter activity, we transiently transfected As4.1 cells with luciferase constructs consisting of different lengths of the REN promoter. HP caused a dose‐dependent reduction in transcriptional activity of the REN promoter. Constructs containing individual mutations in the CREB, HRE, CBF1, and HOXD. PBX binding sites display a reduced baseline activity in some mutants, yet the dose response to HP was preserved, although at a lower magnitude than the original construct. This data suggests that REN gene expression is regulated by oxidative stress. Our results suggest that intercellular calcium levels and TNFα may be involved in mediating HP effect on REN gene expression.