Related Experiment Video

Updated: Mar 20, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
08:45

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors

Published on: July 17, 2020

6.7K

TSH inhibits SERCA2a and the PKA/PLN pathway in rat cardiomyocytes

Jiajia Dong1, Cuixia Gao2, Jing Liu1

  • 1Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, China.

Oncotarget
|May 22, 2016
PubMed

Insights

Elevated thyroid-stimulating hormone (TSH) can impair heart function by reducing calcium handling in heart cells. This study reveals TSH inhibits key proteins, suggesting a mechanism for cardiac dysfunction in subclinical hypothyroidism.

Area of Science:

  • Cardiology
  • Endocrinology
  • Molecular Biology

Background:

  • Subclinical hypothyroidism (sHT) is linked to impaired left ventricular (LV) diastolic and systolic function.
  • Cardiac dysfunction in sHT is associated with altered hemodynamic parameters like increased mean aortic acceleration and pre-ejection/ejection time ratios.

Purpose of the Study:

  • To investigate the direct effects of thyroid-stimulating hormone (TSH) on cardiac function at the molecular level.
  • To elucidate the mechanism by which TSH influences sarcoplasmic reticulum calcium ATPase (SERCA2a) activity and expression in cardiomyocytes.

Main Methods:

  • Primary neonatal rat cardiomyocytes were utilized to study TSH effects.
  • Assays were performed to measure SERCA2a activity and expression.
  • Investigated the role of TSH receptors and the protein kinase A/phospholamban (PKA/PLN) signaling pathway.

Main Results:

  • TSH was found to inhibit both the activity and expression of SERCA2a in cardiomyocytes.
  • TSH exerts its inhibitory effects by binding to cardiomyocyte membrane TSH receptors.
  • The protein kinase A/phospholamban (PKA/PLN) signaling pathway was identified as a key mediator of TSH's inhibitory action.

Conclusions:

  • Increased serum TSH levels directly impact cardiomyocyte function by inhibiting SERCA2a.
  • The TSH-induced inhibition of SERCA2a via the PKA/PLN pathway contributes to cardiac diastolic and systolic dysfunction.
  • Findings suggest a molecular mechanism linking subclinical hypothyroidism to cardiovascular pathologies.
Keywords:
PKAPLNPathology SectionSERCA2aTSHcardiomyocyte

More Related Videos

Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes07:32

Analysis of Cardiac Contractile Dysfunction and Ca2+ Transients in Rodent Myocytes

Published on: May 25, 2022

1.9K
Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes12:49

Isolation, Culture, and Functional Characterization of Adult Mouse Cardiomyoctyes

Published on: September 24, 2013

25.6K

Related Concept Videos

Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
4.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
6.2K