Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników

Znaleziono wyników: 15

Liczba wyników na stronie
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników

Wyniki wyszukiwania

Wyszukiwano:
w słowach kluczowych:  sphingomyelin
help Sortuj według:

help Ogranicz wyniki do:
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
Cross-linking of cell surface receptors by multivalent ligands, e.g. by antibodies, evokes their clustering - patching. Subsequently, these clusters can be translocated by the acto-myosin machinery toward one pole of the cell and assembly cap. Patching of FcγRII in U937 cells correlates with tyrosine phosphorylation of several proteins while cap assembly correlates with their dephosphorylation. To study the mechanism of activation of tyrosine kinases during FcγRII activation we disturbed the organization of the putative plasma membrane microdomains by depletion of membrane cholesterol and sphingomyelin. Cholesterol was removed with the use of β-cyclodextrin while sphingomyelin was decomposed by exogenous sphingomyelinase. Cyclodextrin at 5-10 mM removed about 70% of cholesterol from the cells and abolished the assembly of FcγRII caps thereby arresting the receptors at the patching stage. Similarly, 70 mU/ml sphingomyelinase inhibited cap formation by 60%. Cholesterol and sphingomyelin depletion also suppressed the tyrosine phosphorylation of proteins which accompanied cross-linking of FcγRII. The observations indicate that cholesterol and sphingomyelin can control the interactions of tyrosine kinases with clustered FcγRII.
6
Content available remote

Effect of hypothyreosis on the content of ceramides in rat tissues

84%
Ceramide is the second messenger in the sphingomyelin signalling pathway. A number of extracellular stimuli increase the content of ceramide in the cell. There are some data indicating that the content of ceramide may also be regulated by hormones. The aim of the present study was to examine the effect of hypothyreosis on the content and composition of ceramide in rat tissues. The rats were thyroidectomized and thereafter they received propylthiouracyl in drinking water. The control rats were sham operated. 30 days after thyroidectomy or sham operation the rats were anaesthetized and samples of the liver, white and red vastus lateralis and left ventricle were taken. One set of samples was frozen in liquid nitrogen for analysis of ceramide. Another set of samples was freshly homogenized in chloroform/methanol for further determination of the content of sphingomyelin phosphorous. The content and composition of ceramide-fatty acids was determined by means of gas-liquid chromatography. Twelve ceramides containing different fatty acid residues were identified in both groups. Hypothyreosis reduced the total content of ceramide in each tissue studied: in the heart by 50.9%, in the red vastus by 28.6%, in the white vastus by 29.4% and in the liver by 22%. Concomitantly, the content of individual ceramides was either reduced, stable or even elevated, depending on the tissue. The content of sphingomyelin was elevated in both sections of the vastus lateralis and remained stable in the heart and the liver. The ratio: total content of sphingomyelin to total content of ceramide was elevated in the muscles and remained stable in the liver. This indicates that the reduction in the content of ceramide in the tissues of hypothyroid rats may be a consequence either of a reduction in the formation of ceramide from sphingomyelin, its increased hydrolysis or both. It is concluded that normal thyroid function is needed to maintain the content and composition of ceramide in the tissues.
The sphingomyelin signalling pathway has been shown to function in different skeletal muscle types. The aim of the present study was to examine the effect of endurance training on the functioning of the pathway in the muscles. The experiments were carried out on two groups of male Wistar rats: sedentary and trained for six weeks. 24h after cessation of the training rats were anaesthetized and samples of the soleus, red and white section of the gastrocnemius were taken. The content and composition of sphingomyelin-fatty acids and ceramide - fatty acids was determined by means of gas-liquid chromatography. The content of sphingosine and sphinganine was determined by means of high-pressure liquid chromatography. The activity of neutral Mg++-dependent sphingomyelinase was determined spectophotometrically using trinitrophenylaminolauroyl-sphingomyelin as the substrate. It has been found that training reduces the total content of sphingomyelin- and ceramide-fatty acids, increases the content of sphinganine and does not affect the content of sphingosine in individual muscle types. The activity of the enzyme in the muscles is also elevated. It is concluded that training affects functioning of the sphingomyelin -signalling pathway in skeletal muscles. The reduction in the content of ceramide may contribute to elevation in glucose uptake in skeletal muscles observed after training.
Insulin insufficiency and increased glucose levels are the major features of diabetes type 1 leading to cognitive dysfunctions and neurodegeneration. A reason why different brain structures are characterized by diverse response to increased glucose level is not known. Our previous study showed increased ceramide levels in the brains of rats with diabetes induced by streptozotocin (STZ) injection, which was abolished by myriocin, the inhibitor of serine palmitylotransferase. Ceramides may be important mediators of neuropathological changes and its elevation was found in many brain disorders. The main goal of our present study was to verify if hippocampus, prefrontal cortex and cerebellum response differently to hyperglycemia/hypoinsulinemia in terms of changes in sphingolipids concentrations. We attempted to identify potential source of ceramides by measuring the sphingomyelinase concentrations and by blocking the ceramide de novo synthesis pathway. We found that in cerebellum and hippocampus of hyperglycemic animals sphingolipids concentrations underwent subtle modifications while prefrontal cortex exhibited massive changes in ceramides and SMs content. Total ceramide levels was significantly elevated in prefrontal cortex of diabetic rats, which was reduced by myriocin, while rats exposed to STZ showed only small increase of total SM in this brain structure. The increased content of ceramides containing SAFAs (saturated fatty acids) in prefrontal cortex was diminished by myriocin. SAFA-contained SMs did not present changes. Elevation of MUFA- (monounsaturated fatty acids), and PUFA-ceramides (polyunsaturated fatty acids) in prefrontal cortex of STZ-treated rats was reduced by myriocin, similarly as MUFA-SMs augmentation. PUFA-ceramides and PUFA-SMs experienced only slight modifications. Both – ceramides and omega-6 – SMs increased dramatically and were downregulated by myriocin. We conclude that the prefrontal cortex may be particularly sensitive to hyperglycemic conditions and hypoinsulinemia. Moreover, the novo synthesis seems to be an important pathway of ceramide generation since usage of myriocin strongly reduced ceramide levels enhanced by STZ injection. Augmentation in ceramide content was correlated with enhancement of SMs production. These unexpected results may be explained by the incorporation of redundant ceramides into SMs, a mechanism by which the toxic level of ceramides is reduced in the brain. Supported by grant 123-27575 P from the State Committee for Scientific Research, Warsaw, Poland
The apoptotic response of the immature B-cell to the cross-linking of surface IgM receptors provides a good model for cell death and we show in WEHI-231 B-cells that the time course of apoptosis corresponds to the increased formation of ceramide, as measured either by mass (using the diacylglycerol kinase method) or radiolabelling with [3H]palmitate. Inhibitors of sphingosine biosynthesis have no effect on cell death induced by anti-IgM in WEHI-231 but inhibitors of ceramidase accelerate apoptosis, suggesting that activation of sphingomyelinase is the key event in apoptosis. We have demonstrated this by in vitro assay of neutral sphingomyelinase. Apoptosis is also important in normal brain development and neuronal survival is dependent upon phosphatidylinositol 3-kinase (PI3-kinase) activation by growth factors (insulin, nerve growth factor etc.). Withdrawal of these growth factors or inhibition of PI3-kinase with wortmannin or LY294002 activated the pro-apoptotic CPP32 (Yama/Apopain/caspase 3, EC 3.4.22), activated neutral sphingomyelinase and increased ceramide formation in an immortalized dorsal root ganglion cell line F-11. Protection against apoptosis can be achieved by overexpression of the bcl2 family of proteins or addition of drugs which elevate cAMP levels. cAMP protects against apoptosis induced by either wortmannin or staurosporine. The specificity for cAMP was confirmed by showing protection with the specific agonist (Sp)cAMPS and increased killing with the antagonist (Rp)cAMPS. However, cAMP did not protect against ceramide killing, suggesting that there are at least two major pathways of apoptosis in neuronal cells.
Nematodes were found to synthesize phosphorylcholine-containing molecules not present in higher organisms, i.e. phosphorylcholine-substituted glycosphingolipids and (glyco)proteins. Investigations on the biosynthesis of these structures provided first biochemical evidence for the presence of the Kennedy and Bremer-Greenberg pathways in the model organism Caenorhabditis elegans.
Pierwsza strona wyników Pięć stron wyników wstecz Poprzednia strona wyników Strona / 1 Następna strona wyników Pięć stron wyników wprzód Ostatnia strona wyników
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.