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Oxidative stress upregulates renal Angiotensin II type I receptors via activation of transcription factor nuclear factor‐kappaB
Author(s) -
Javkhedkar Apurva Arvind,
Banday Anees Ahmad,
Lokhandwala Mustafa F
Publication year - 2009
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.23.1_supplement.lb149
Subject(s) - angiotensin ii receptor type 1 , oxidative stress , pyrrolidine dithiocarbamate , angiotensin ii , transcription factor , receptor , downregulation and upregulation , endocrinology , medicine , chemistry , microbiology and biotechnology , signal transduction , biology , nf κb , biochemistry , gene
Regulation of redox homeostasis is associated with normal functioning of cells, whereas oxidative stress is seen with various cardiovascular disorders like hypertension. Angiotensin II (Ang II), acting via Ang II type I (AT1) receptors, has known effects on the renal proximal tubular sodium transport, thus plays an important role in regulating blood pressure. Oxidative stress is also known to activate redox sensitive transcription factor NF‐kappaB and evidences indicate that AT1 receptor gene posses binding site for this transcription factor. Herein, we aim to investigate if oxidative stress upregulates renal AT1 receptors through NF‐kappaB activation. Human proximal tubular (HK‐2) cells were incubated with a pro oxidant L‐buthionine sulfoximine (BSO), an inhibitor of glutathione, for 48 hrs. Results Compared to control, there was an increase in levels of protein nitrotyrosination indicating oxidative stress in BSO treated HK‐2 cells. There was also activation of NF‐kappaB, upregulation of AT1 receptor protein, and increased Ang II‐induced Ca 2+ signaling. Furthermore, treatment with pyrrolidine dithiocarbamate, a NF‐kappaB inihibitor, blocked NF‐kappaB activation, abolished AT1 receptor upregulation and exaggerated Ang II induced Ca 2+ signaling. Conclusion These results suggest that oxidative stress upregulates renal AT1 receptors via activation of transcription factor NF‐kappaB. Grant: AHA‐SDG‐0835428N