Long- and short-term effects of thyroxine on sphingolipid metabolism in rat liver.
BACKGROUND
Thyroid hormones are well known as modulators of signal transduction. Early experiments showed that sustained elevation of diacylglycerol (DAG) and ceramide levels in liver cells of hypothyroid rats is an essential prerequisite for disturbances in agonist responsiveness of hepatocytes. In this paper the effects of thyroxine (L-T(4)) on sphingolipid mass, synthesis, and degradation are investigated.


METHODS
The experiments were performed on either [1(14)C]CH(3)COOH-labeled rat liver or hepatocytes and isolated liver cell plasma membranes. To determine sphingolipid synthesis and degradation in the liver, [(14)C]palmitic acid, [methyl-(14)C]-labeled sphingomyelin (SM), and phosphatidylcholine were used.


RESULTS
The administration of L-T(4) to animals was accompanied by a time-dependent accumulation of newly synthesized ceramide, glucosyl ceramide, and SM in liver. In hyperthyroid liver, prominent ceramide accumulation and acidic SMase activation was found. The addition of hormone in a physiological dose to the incubation or perfusion medium led to a rapid stimulation of de novo ceramide synthesis, transient lipid accumulation in the liver, followed by SM synthase activation.


CONCLUSIONS
Our results indicate that SMases, ceramide synthesis de novo, and SM synthase are under thyroid hormone control. The level of ceramide is markedly elevated in the hyperthyroid liver via the activation of acidic SMase and lipid synthesis de novo. In experiments in vitro, the hormone induces a short-lived accumulation of sphingolipid, probably due to its reduced efflux from the liver.
Babenko
Nataliya A
NA
Department of Physiology of Ontogenesis, Institute of Biology, Kharkov Karazin National University, Ukraine. babenko@univer.kharkov.ua
D000818:Animals; D002518:Ceramides / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010713:Phosphatidylcholines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism; D013974:Thyroxine / Q000494:pharmacology*
D002518:Ceramides; D010713:Phosphatidylcholines; D013107:Sphingolipids; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase; D013974:Thyroxine