Rapid stimulation in vitro of rat liver cytochrome oxidase activity by 3,5-diiodo-L-thyronine and by 3,3'-diiodo-L-thyronine
Abstract
The effect of the iodothyronines (thyroxine (T4), 3,5,3'-triiodo-L-thyronine (L-T3), 3,5-diiodo-L-thyronine (3,5-T2), 3,3'-diiodo-L-thyronine (3,3'-T2), 3',5'-diiodo-L-thyronine (3',5'-T2), 3'-monoiodo-L-thyronine (3'-T1), 3-monoiodo-L-thyronine (3-T1) and thyronine (T0)) on rat liver cytochrome oxidase (COX) activity after their addition to rat liver homogenate and isolated mitochondria from normal and hypothyroid rats has been investigated. The addition of 3,3'-T2 and 3,5-T2 (T2s) to the liver homogenate from hypothyroid rats, but not from normal rats, significantly enhanced COX activity. The addition of T3 had a remarkably lower effect that was almost completely abolished when the propylthiouracil (PTU), an inhibitor of the type I deiodinase activity, was also added to the incubation mixture. After the addition of T2s the maximum effect was obtained at a concentration of about 10(-6) M for both 3,3'-T2 and 3,5-T2, while a 50% increase was obtained at a concentration of about 10(-9) M in both cases. The effects of T2s were rapid and already evident after 5 min of incubation (+40-50%). The maximal effect was reached after only 30 min of incubation. The above effects were not observed after the addition of T2s to the isolated mitochondria. The results clearly demonstrate that both 3,3'-T2 and 3,5-T2 directly stimulate mitochondrial COX activity which is possibly achieved through a cytoplasmic factor. The addition of the other iodothyronines (T4, 3',5'-T2, 3'-T1, 3-T1 and T0).
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In vivo data from experimental animal models and human studies, where PTU has been administered, resulted in lower 3,5-T2 concentrations compared to appropriate controls.
“In contrast, in vivo data from experimental animal models and human studies, where PTU has been administered, resulted in lower 3,5-T2 concentrations compared to appropriate controls.”
From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [52]
Various attempts to demonstrate the reaction of 3,5-T2 formation from T3 in vitro failed to support the hypothesis.
“Circumstantial evidence using the DIO1 inhibitor PTU in isolated rat mitochondria or perfused rat liver led to the assumption that 3,5-T2 is a logical deiodinase product of T3 (16, 52), but various attempts to demonstrate such a reaction in vitro failed to support this hypothesis.”
From 3,5-T2—A Janus-Faced Thyroid Hormone Metabolite Exerts Both Canonical T3-Mimetic Endocrine and Intracrine Hepatic Action (2020) · cites this paper as [52]
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- Authors
- Lanni, A., Moreno, M., Lombardi, A., & Goglia, F.
- Affiliations
- University of Naples Federico II (IT)
- Corresponding author
- Goglia, F.
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 1994-02
- Volume
- 99
- Issue
- 1
- Pages
- 89-94
- ISSN
- 0303-7207 (ISSN-L)
- OpenAlex
- W1965321242
- Cited by
- 58
- References
- 0
- Citations by year
- 2022: 3 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 5
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular and Cellular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi della Campania "Luigi Vanvitelli" (submittedVersion)
- Funders
- Centre National de la Recherche Scientifique
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Biochemical Acid Research Studies
- Keywords
- cytochrome c oxidase, iodothyronines, 3,5-diiodo-L-thyronine, triiodothyronine, thyroxine, hypothyroidism, liver mitochondria, type I deiodinase, propylthiouracil, thyroid hormone stimulation, rat liver
- MeSH terms
- Animals, Body Weight, Electron Transport Complex IV, Diiodothyronines, Energy Metabolism, Enzyme Activation, Hypothyroidism, Iodide Peroxidase, Liver, Male, Mitochondria, Liver, Organ Size, Triiodothyronine, Rats, Wistar, Rats
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