title: TSH inhibits SERCA2a and the PKA/PLN pathway in rat cardiomyocytes.
abstract: Elevated thyroid-stimulating hormone (TSH) levels often accompany impaired LV diastolic function and subtle systolic dysfunction in subclinical hypothyroidism (sHT). These cardiac dysfunctions are characterized by increases in mean aortic acceleration and pre-ejection/ejection time ratios. To explore the mechanism underlying these pathologies, we investigated the effects of TSH on sarcoplasmic reticulum calcium ATPase (SERCA2a) activity and expression in neonatal rat cardiomyocytes. TSH inhibited SERCA2a activity and expression by binding to TSH receptors in cardiomyocyte membranes and inhibiting the protein kinase A/phoshpolamban (PKA/PLN) signaling pathway. These results suggest that increases in serum TSH levels contribute to the development of cardiac diastolic and systolic dysfunction.
authors.affiliation: Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Ultrasonic Diagnosis, Gansu Provincial Hospital, Lanzhou, Gansu, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Gansu Provincial Hospital, Lanzhou, Gansu, China.
authors.forename: Yunshan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Tian
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000473:pathology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D003971:Diastole; D007037:Hypothyroidism / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction; D013599:Systole; D013972:Thyrotropin / Q000097:blood / Q000502:physiology*; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013972:Thyrotropin; D000099211:Phospholamban
keywords: PKA; PLN; Pathology Section; SERCA2a; TSH; cardiomyocyte