ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Neuronal hypoxia induces Hsp40-mediated nuclear import of type 3 deiodinase as an adaptive mechanism to reduce cellular metabolism.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 59 citations in OpenAlex.
- Guidelines for the treatment of hypothyroidism: prepared by the american thyroid association task force on thyroid hormone replacement.Thyroid : official journal of the American Thyroid Association · 2014Guideline
- American Thyroid Association Guide to investigating thyroid hormone economy and action in rodent and cell models.Thyroid : official journal of the American Thyroid Association · 2014Guideline
- Treatment with thyroxine restores myelination and clinical recovery after intraventricular hemorrhage.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Trial
- DIO3 associates with sorting nexins and endosomal trafficking networks in ovarian cancer.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Genetics of ischemic stroke functional outcome.Journal of neurology · 2024Review
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- Selpercatinib-Induced Hypothyroidism Through Off-Target Inhibition of Type 2 Iodothyronine Deiodinase.JCO precision oncology · 2022Article
- Effects of Thyroid Hormone on Tissue Hypoxia: Relevance to Sepsis Therapy.Journal of clinical medicine · 2021Review
- Deiodinases and the Metabolic Code for Thyroid Hormone Action.Endocrinology · 2021Review
- Temporal Pole Responds to Subtle Changes in Local Thyroid Hormone Signaling.Journal of the Endocrine Society · 2020Article
- Paradigms of Dynamic Control of Thyroid Hormone Signaling.Endocrine reviews · 2019Review
- Type 2 deiodinase polymorphism causes ER stress and hypothyroidism in the brain.The Journal of clinical investigation · 2019Article
- Induction of Type 2 Iodothyronine Deiodinase After Status Epilepticus Modifies Hippocampal Gene Expression in Male Mice.Endocrinology · 2018Article
- Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury.Pharmacology & therapeutics · 2018Review
- The Deiodinase Trio and Thyroid Hormone Signaling.Methods in molecular biology (Clifton, N.J.) · 2018Review
- Glycinergic Input to the Mouse Basal Forebrain Cholinergic Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Hypothyroidism.Lancet (London, England) · 2017Review
- Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Thyroid Hormone Signaling in Oligodendrocytes: from Extracellular Transport to Intracellular Signal.Molecular neurobiology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
In neurons, the type 3 deiodinase (D3) inactivates thyroid hormone and reduces oxygen consumption, thus creating a state of cell-specific hypothyroidism. Here we show that hypoxia leads to nuclear import of D3 in neurons, without which thyroid hormone signaling and metabolism cannot be reduced. After unilateral hypoxia in the rat brain, D3 protein level is increased predominantly in the nucleus of the neurons in the pyramidal and granular ipsilateral layers, as well as in the hilus of the dentate gyrus of the hippocampal formation. In hippocampal neurons in culture as well as in a human neuroblastoma cell line (SK-N-AS), a 24 h hypoxia period redirects active D3 from the endoplasmic reticulum to the nucleus via the cochaperone Hsp40 pathway. Preventing nuclear D3 import by Hsp40 knockdown resulted an almost doubling in the thyroid hormone-dependent glycolytic rate and quadrupling the transcription of thyroid hormone target gene ENPP2. In contrast, Hsp40 overexpression increased nuclear import of D3 and minimized thyroid hormone effects in cell metabolism. In conclusion, ischemia/hypoxia induces an Hsp40-mediated translocation of D3 to the nucleus, facilitating thyroid hormone inactivation proximal to the thyroid hormone receptors. This adaptation decreases thyroid hormone signaling and may function to reduce ischemia-induced hypoxic brain damage.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.