Regulation of AT1R expression through HuR by insulin.

Nucleic Acids Research
Kirsi PaukkuJukka Y A Lehtonen

Abstract

Angiotensin II type 1 receptor (AT1R) has a pathophysiological role in hypertension, atherosclerosis and heart failure. Type 2 diabetes is hyperinsulinemic state and a major risk factor for atherosclerosis and hypertension. It is known that hyperinsulinemia upregulates AT1R expression post-transcriptionally by increasing the half-life of AT1R mRNA, but little is known about the mechanism of this effect. In the present study, we first identified AT1R 3'-UTR as a mediator of insulin effect. Using 3'-UTR as a bait, we identified through analysis of insulin-stimulated cell lysates by affinity purification and mass spectrometry HuR as an insulin-regulated AT1R mRNA binding protein. By ribonucleoprotein immunoprecipitation, we found HuR binding to AT1R to be increased by insulin. Overexpression of HuR leads to increased AT1R expression in a 3'-UTR-dependent manner. Both insulin and HuR overexpression stabilize AT1R 3'-UTR and their responsive element within 3'-UTR are located within the same region. Cell fractionation demonstrated that insulin induced HuR translocation from nucleus to cytoplasm increased HuR binding to cytoplasmic AT1R 3'-UTR. Consistent with HuR translocation playing a mechanistic role in HuR effect, a reduction in ...Continue Reading

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Citations

Apr 5, 2014·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Sarah E Brennan-LaunBret A Hassel
Sep 10, 2013·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Zoltan VamosAkos Koller
Aug 13, 2014·Medical Oncology·Ioly Kotta-LoizouStamatios Theocharis
Dec 19, 2015·Nucleic Acids Research·Michael BacklundJukka Y A Lehtonen
Mar 25, 2015·Trends in Cardiovascular Medicine·Sahana Suresh BabuPrasanna Krishnamurthy
Jun 7, 2018·Physiological Reviews·Steven J ForresterSatoru Eguchi
Jan 17, 2019·Database : the Journal of Biological Databases and Curation·Martyna NowackaStanislaw Dunin-Horkawicz
Jan 17, 2014·American Journal of Physiology. Renal Physiology·Rudolf Pullmann, Hamid Rabb
Apr 25, 2019·International Journal of Molecular Sciences·Cosmin Cătălin MustăciosuBeatrice Mihaela Radu
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Sep 16, 2017·Acta Biochimica Et Biophysica Sinica·Jin Shang, Zhanzheng Zhao
Feb 21, 2021·Clinica Chimica Acta; International Journal of Clinical Chemistry·Wujun ChenDongming Xing
May 28, 2019·Metabolism: Clinical and Experimental·Randall L MynattJaycob D Warfel

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Methods Mentioned

BETA
immunoprecipitation
affinity purification
transfection
PCR
electrophoretic mobility-shift assay
Infrared Imaging

Software Mentioned

Mascot® Peptide Mass Fingerprint Ion Search
REMSA

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