Delineation of three different thyroid hormone-response elements in promoter of rat sarcoplasmic reticulum Ca2+ATPase gene. Demonstration that retinoid X receptor binds 5' to thyroid hormone receptor in response element 1.

Hartong, R.; Wang, Naishu; Kurokawa, Riki; Lazar, MA; Glass, Chris K.; Apriletti, James W.; Dillmann, Wolfgang H.

doi:10.1016/s0021-9258(18)99978-3

Cited by 100 publications

(9 citation statements)

References 59 publications

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“…We sought to determine whether expression of critical TT/SR proteins were directly regulated by T3 and thus provide a mechanism by which T-tubule structure, function and EC coupling are altered in TH-deficient conditions that includes heart failure. T3-responsive Myh6, Myh7 and SERCa2 genes [44,45] were altered as expected in TH-deficient PTU hearts and the T3 dose [34] was sufficient to reverse these changes (Fig. 5A).…”

Section: T3 Regulates Tt and Sr Structural And Functional Genessupporting

confidence: 69%

“…Analysis of known T3-responsive myosin heavy chain (MHC) genes showed the expected significant reduction in α-MHC mRNA (Myh6) and increase in β-MHC mRNA (Myh7) with thyroid deficiency (PTU), and subsequent normalization with T3 treatment [42][43][44]. Expression of known T3responsive SR Ca 2+ ATPase (SERCa2) was similarly decreased in PTUtreated hearts, and T3 treatment increased to EU values [45]. Among other calcium-regulatory/channel proteins, phospholamban (PLN) and ryanodine receptor (RyR2) mRNAs remained unchanged in response to changes in thyroid condition, while Ca v 1.2 (LTCC) mRNA increased (p < 0.01) in the thyroid deficient PTU-treated hearts.…”

Section: Expressed Gene Analysis By Rt-pcr and Rnaseqmentioning

confidence: 99%

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Triiodothyronine maintains cardiac transverse-tubule structure and function

Gilani

Wang

Muncan

et al. 2021

Journal of Molecular and Cellular Cardiology

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Subclinical hypothyroidism and low T3 syndrome are commonly associated with an increased risk of cardiovascular disease (CVD) and mortality. We examined effects of T3 on T-tubule (TT) structures, Ca 2+ mobilization and contractility, and clustering of dyadic proteins.Thyroid hormone (TH) deficiency was induced in adult female rats by propyl-thiouracil (PTU; 0.025%) treatment for 8 weeks. Rats were then randomized to continued PTU or triiodo-L-thyronine (T3; 10 μg/kg/d) treatment for 2 weeks (PTU + T3). After in vivo echocardiographic and hemodynamic recordings, cardiomyocytes (CM) were isolated to record Ca 2+ transients and contractility. TT organization was assessed by confocal microscopy, and STORM images were captured to measure ryanodine receptor (RyR2) cluster number and size, and L-type Ca 2+ channel (LTCC, Ca v 1.2) co-localization. Expressed genes including two integral TT proteins, junctophilin-2 (Jph-2) and bridging integrator-1 (BIN1), were analyzed in left ventricular (LV) tissues and cultured CM using qPCR and RNA sequencing. The T3 dosage used normalized serum T3, and reversed adverse effects of TH deficiency on in vivo measures of cardiac function. Recordings of isolated CM indicated that T3 increased rates of Ca 2+ release and re-uptake, resulting in increased velocities of sarcomere shortening and re-lengthening. TT periodicity was significantly decreased, with reduced transverse tubules but increased longitudinal tubules in TH-deficient CMs and LV tissue, and these structures were normalized by T3 treatment. Analysis of STORM data of PTU myocytes showed decreased RyR2 cluster numbers and RyR localizations within each cluster without significant changes in Ca v 1.2 localizations within RyR clusters. T3 treatment normalized RyR2 cluster size and number. qPCR and RNAseq analyses of LV and cultured CM showed that Jph2 expression was T3-responsive, and its increase with treatment may explain improved TT organization and RyR-LTCC coupling.

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Section: T3 Regulates Tt and Sr Structural And Functional Genessupporting

confidence: 69%

Section: Expressed Gene Analysis By Rt-pcr and Rnaseqmentioning

confidence: 99%

Triiodothyronine maintains cardiac transverse-tubule structure and function

Gilani

Wang

Muncan

et al. 2021

Journal of Molecular and Cellular Cardiology

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“…Along these lines, we recently found that total T3 in plasma correlated strongly with maximum oxygen consumption (peak VO2) in patients with dilated cardiomyopathy, as assessed by cardiorespiratory stress testing [3]. Furthermore, low T3 plasma levels appear to be an independent risk factor for increased mortality and morbidity in patients with heart failure [73], and low TH levels after infarction increase mortality in patients with acute myocardial infarction [32].…”

Section: Clinical Implications:protection Vs Functionmentioning

confidence: 94%

“…Το γονίδιο που κωδικοποιεί τη σαρκοπλασματική Ca 2+ -ATPάση (SERCa2) έχει τρεις θέσεις δράσης της T3 (30)(31)(32). Η αποδέσμευση του ασβεστίου και η επαναχρησιμοποίησή του στο σαρκοπλασματικό δίκτυο αποτελούν σημαντικούς παράγοντες ρύθμισης της συσταλτικότητας και της διαστολικής χάλασης του μυοκρδίου (33).…”

Section: α12 γενομικη ∆ραση των θυρεοει∆ικων ορμονων στο μυοκαρ∆ιοunclassified

“…This response is thought to contribute to energy preservation and, thus, to protection under stress. Patients with low TH levels at the onset of infarction to have smaller infarctions [32]. Furthermore, tissue hypothyroidism during cardiac remodeling increases tolerance of the postischemic myocardium to ischemia [33].…”

Section: Clinical Implications:protection Vs Functionmentioning

confidence: 99%

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Προστασία Του Υποθυρεοειδικού Μυοκαρδίου Απέναντι Στην Ισχαιμία

Sfakianoudis¹,

Σφακιανούδης²

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Η παρούσα μελέτη αναζήτησε την ανταπόκριση της υποθυρεοειδικής καρδιάς στην ισχαιμία-επαναιμάτωση. Υποθυρεοειδισμός προκλήθηκε μετά από του στόματος χορήγηση για 3 εβδομάδες προπυλθειουρακίλης ενώ ευθυρεοειδικά ποντίκια χρησιμοποιήθηκαν ως μάρτυρες. Απομονωμένες καρδιές τόσο από υποθυρεοειδικά όσο και απο ευθυρεοειδικά ποντίκια υπεβλήθησαν σε πρωτόκολλο ισχαιμικής ροής το οποίο δισδέχτηκε φάση επαναιμάτωσης. Η αποκατάσταση της λειτουργικότητας της αριστερής κοιλίας καθώς και το επίπεδο έκφρασης των πρωτεινικών κινασών PKCE και PKCΔ αλλά και τα επίπεδα φωσφορυλίωσης της p46 and p54 c-jun NH(2)-terminal kinases (JNKs) απέναντι στη ισχαιμία-επαναιμάτωση αποτέλεσαν τα σημεία της μελέτης. Η συστατλτικότητα της αριστερής κοιλίας ήταν σημαντικά βελτιωμένη αλλά και η PKC ε ήταν 1.4 φορές υψηλότερη στις υποθυρεοειδικές καρδιές σε σχέση με τα controls ενώ η PKC δ δε φαίνεται να επηρεάζεται. Επιπλέον, τα επίπεδα φωσφορυλίωσης της p46 and p54 c-jun ήταν 2.2 και 2.6 φορές υψηλότερα σε φάση ηρεμίας στις υποθυρεοεδικές σε σχέση με τις ευθυρειεδικιές γεγονός το οποίο δεν επαναλαμβάνεται μετά την ισχαιμία επαναιμάτωση όπου οι υποθευρεοειδικές καρδιές δεν αυξάνουν τα επίπεδα φωσφορυλίωσης των συγκεκριμένων κινασών ενώ οι ευθυρεοειδικές καρδιές τα εκτοξέυουν 5.5 και 6 φορές πάνω.

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On the Trail of Thyroid Hormone Receptor Epigenetics

Sarkar

2017

Gene Regulation, Epigenetics and Hormone Signaling

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Delineation of three different thyroid hormone-response elements in promoter of rat sarcoplasmic reticulum Ca2+ATPase gene. Demonstration that retinoid X receptor binds 5' to thyroid hormone receptor in response element 1.

Cited by 100 publications

References 59 publications

Triiodothyronine maintains cardiac transverse-tubule structure and function

Triiodothyronine maintains cardiac transverse-tubule structure and function

Προστασία Του Υποθυρεοειδικού Μυοκαρδίου Απέναντι Στην Ισχαιμία

On the Trail of Thyroid Hormone Receptor Epigenetics

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