Hyperthyroidism Evokes Myocardial Ceramide Accumulation

Abstract

Background: Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. Methods: Male Wistar rats were treated for 10 days with triiodothyronine (T₃) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. Results: We have demonstrated that prolonged, in vivo, T₃ treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), β-hydroxyacyl-CoA dehydrogenase (β-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). Conclusions: We conclude that prolonged T₃ treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.

Sphingolipid Mediators of Myocardial Pathology

“…Prolonged treatment with T 3 led to a prominent increase of DHS, sphingosine, ceramide and SM levels, but decreased S1P levels, in cardiomyocytes taken from the LV of male mice. 66 Consistent with this, data demonstrated that T 3 treatment reduced the activity of nSMase, but caused no change in ceramidase activity, which would be required to generate sphingosine as a substrate for SphKs. 66 …”

“… 66 Consistent with this, data demonstrated that T 3 treatment reduced the activity of nSMase, but caused no change in ceramidase activity, which would be required to generate sphingosine as a substrate for SphKs. 66 …”

Changes in the Diaphragm Lipid Content after Administration of Streptozotocin and High-Fat Diet Regime

“…Routine Western blotting procedures were used to detect protein content as described previously [ 38 – 40 ]. The samples were homogenized in ice-cold RIPA (radioimmunoprecipitation assay) buffer (50 mM Tris-HCl, 150 M NaCl, 1 mM EDTA, 1% NP-40, 0.25% Na-deoxycholate, 1 mM phenylmethylsulfonyl fluoride, 1 μ g/ml aprotinin, 1 μ g/ml leupeptin, 1 μ g/ml pepstatin, 1 mM sodium orthovanadate, and 1 mM sodium fluoride) for 1 min at 4°C.…”

Effects of Long-Term Calcium Supplementation on Rats Bone Mineral Density and Cardiovascular Based on Metabonomics

“…A variety of sphingolipids were derived from the sphingosine backbone (21). Sphingosine itself also plays a unique role in the formation of 1-sphingosine (S1P), which is a marker of atherosclerosis after binding to HDL-C (22). Sphingosine and its derivatives play a role to prevent a variety of lipid deposition, vascular intimal focal fibrosis after combination with HDL-C (23).…”