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Citations to this article

Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats
Warner S. Simonides, … , Antonio C. Bianco, Stephen A. Huang
Warner S. Simonides, … , Antonio C. Bianco, Stephen A. Huang
Published February 7, 2008
Citation Information: J Clin Invest. 2008;118(3):975-983. https://doi.org/10.1172/JCI32824.
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Research Article Endocrinology Article has an altmetric score of 4

Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats

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Abstract

Thyroid hormone is a critical determinant of cellular metabolism and differentiation. Precise tissue-specific regulation of the active ligand 3,5,3′-triiodothyronine (T3) is achieved by the sequential removal of iodine groups from the thyroid hormone molecule, with type 3 deiodinase (D3) comprising the major inactivating pathway that terminates the action of T3 and prevents activation of the prohormone thyroxine. Using cells endogenously expressing D3, we found that hypoxia induced expression of the D3 gene DIO3 by a hypoxia-inducible factor–dependent (HIF-dependent) pathway. D3 activity and mRNA were increased both by hypoxia and by hypoxia mimetics that increase HIF-1. Using ChIP, we found that HIF-1α interacted specifically with the DIO3 promoter, indicating that DIO3 may be a direct transcriptional target of HIF-1. Endogenous D3 activity decreased T3-dependent oxygen consumption in both neuronal and hepatocyte cell lines, suggesting that hypoxia-induced D3 may reduce metabolic rate in hypoxic tissues. Using a rat model of cardiac failure due to RV hypertrophy, we found that HIF-1α and D3 proteins were induced specifically in the hypertrophic myocardium of the RV, creating an anatomically specific reduction in local T3 content and action. These results suggest a mechanism of metabolic regulation during hypoxic-ischemic injury in which HIF-1 reduces local thyroid hormone signaling through induction of D3.

Authors

Warner S. Simonides, Michelle A. Mulcahey, Everaldo M. Redout, Alice Muller, Marian J. Zuidwijk, Theo J. Visser, Frank W.J.S. Wassen, Alessandra Crescenzi, Wagner S. da-Silva, John Harney, Felix B. Engel, Maria-Jesús Obregon, P. Reed Larsen, Antonio C. Bianco, Stephen A. Huang

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2013 2012 2011 2010 2009 2008 Total
Citations: 3 4 12 4 9 4 14 7 6 9 5 9 4 7 10 4 5 5 121
Citation information
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Citations to this article in year 2021 (9)

Title and authors Publication Year
Deiodinase-3 is a thyrostat to regulate podocyte homeostasis
S Agarwal, KH Koh, NJ Tardi, C Chen, RR Dande, JP WerneckdeCastro, YR Sudhini, C Luongo, D Salvatore, B Samelko, MM Altintas, S Mangos, A Bianco, J Reiser
EBioMedicine 2021
Deiodinases and the Metabolic Code for Thyroid Hormone Action
SC Russo, F Salas-Lucia, AC Bianco
Endocrinology 2021
Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions
L Sabatino, C Vassalle, CD Seppia, G Iervasi
Endocrinology and Metabolism 2021
The Impact of Selenium Deficiency on Cardiovascular Function
BK Shimada, N Alfulaij, LA Seale
International journal of molecular sciences 2021
Deiodinases and Cancer
A Nappi, MA Stefano, M Dentice, D Salvatore
Endocrinology 2021
The Type 3 Deiodinase Is a Critical Modulator of Thyroid Hormone Sensitivity in the Fetal Brain
ME Martinez, A Hernandez
Frontiers in neuroscience 2021
Thyroid function in the subacute phase of traumatic brain injury: a potential predictor of post-traumatic neurological and functional outcomes
C Mele, L Pagano, D Franciotta, M Caputo, A Nardone, G Aimaretti, P Marzullo, V Pingue
Journal of Endocrinological Investigation 2021
Combined use of low T3 syndrome and NT-proBNP as predictors for death in patients with acute decompensated heart failure
X Zhao, R Zhang, H Jiang, K Liu, C Ma, M Bai, T An, Y Yao, X Wang, M Wang, Y Li, Y Zhang, J Zhang
BMC Endocrine Disorders 2021
Effects of Thyroid Hormone on Tissue Hypoxia: Relevance to Sepsis Therapy
Lourbopoulos AI, Mourouzis IS, Trikas AG, Tseti IK, Pantos CI
Journal of Clinical Medicine 2021

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