Effect Of Sphingomyelinase Research Articles

The relationship of sphingolipid mechanisms with oxidative stress and changes in mitochondria during functional unloading of postural muscles

Background. Prolonged inactivity of skeletal muscles is accompanied by the development of oxidative stress and changes in sphingolipid metabolism. The relationship of sphingolipid mechanisms with generation of reactive oxygen species (ROS) in muscles subjected to functional unloading has not been studied.The aim. To identify the relationship between changes in sphingomyelinase and ceramide abundance and ROS production in rat soleus muscle during functional unloading.Methods. Male Wistar rats were subjected to hindlimb suspension for 12 hours or 14 days with the acid sphingomyelinase (ASM) inhibitor amitriptyline (AMI). The levels of ASM, ceramide and ROS were determined by fluorescence microscopy on histological sections. Pro-oxidant enzymes (NADPH oxidases 2 and 4 (NOX2 and NOX4)), cytochrome c oxidase (COX IV), the regulator of mitochondrial biogenesis PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) in muscle homogenates were studied by Western blotting, which also was used for assessment of ceramide and ASM in the isolated mitochondrial fraction. The effects of sphingomyelinase and prooxidants on ceramide, ASM, ROS and NOX2 levels were studied in an ex vivo model by incubating the muscle with exogenous sphingomyelinase or H2O2.Results. 12-hour hindlimb suspension was accompanied by an increase in the level of ASM and ceramide in rat soleus muscle. Unloading for 14 days was characterized by an increase in ASM, ceramide, ROS, NOX2, NOX4 and a decrease in COX IV and PGC-1α levels. ASM and ceramide were also increased in the mitochondrial fraction of muscle. The ASM inhibitor amitriptyline partially or completely prevented the changes caused by the unloading. In the ex vivo model, the stimulating effect of exogenous sphingomyelinase on the ROS and NOX2 levels in rat soleus muscle was found, whereas H2O2 stimulated muscle ASM and ceramide production.Conclusion. A close relationship has been established between the sphingomyeli-nase pathway of ceramide formation and ROS production in skeletal muscle under conditions of functional unloading.

Effect of sphingomyelinase on TRP ion channel activation of trigeminal sensory neurons and transfected cell line

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P-79 - Effect of sphingomyelinase and ceramide on the tyrosine phosphorylation of intracellular proteins.

P-79 - Effect of sphingomyelinase and ceramide on the tyrosine phosphorylation of intracellular proteins.

O-189 - Effect of sphingomyelinase on interferon-γ-induced HL-60 cell differentiation.

O-189 - Effect of sphingomyelinase on interferon-γ-induced HL-60 cell differentiation.

Modulation of sphingomyelinase-induced cholesterol esterification in fibroblasts, CaCo 2 cells, macrophages and smooth muscle cells

The present study has focused on three questions concerning the effect of sphingomyelinase on release of free cholesterol from the plasma membrane and its intracellular translocation: (i) Can one change the direction of the flow of cholesterol? (ii) Can one modulate the flow? (iii) May such a mechanism be relevant in atherogenesis? (i) The results obtained show that even in the presence of potent nonlipoprotein cholesterol acceptors in the medium, the intracellular flow of cholesterol is not reduced as measured by cholesterol esterification. Moreover, in sphingomyelinase-treated cells, cholesterol efflux in presence of nonlipoprotein acceptors was not enhanced even when intracellular esterification was inhibited. (ii) Modulation of the sphingomyelinase induced cholesterol flow can be obtained by 100 μM verapamil which reduces it. In human skin fibroblast, interference with the delivery of free cholesterol to its site of esterification was found in the presence of brefeldin A. (iiI) Aortic smooth muscle cells in culture are sensitive to low concentrations of sphingomyclinase and the increase in esterified cholesterol is evident also after exposure to the enzyme for 24 h. The present results suggest that in the plasma membrane, free cholesterol bound to sphingomyelin may be in a compartment which renders it more available for transport to the cell interior than for efflux. In view of the sensitivity of aortic smooth muscle cells to sphingomyelinase, this mechanism for enhanced esterification of cholesterol could be relevant to the transformation of arterial smooth muscle cells into foam cells in the process of atherogenesis.

Effect of sphingomyelinase from Clostridium perfringens on the metabolic activity and phospholipid composition of thyroid slices

Sphingomyelinase, like thyroid-stimulating hormone, increases the oxidation of [1- 14C]glucose to 14CO 2 and the incorporation of 32P i into phospholipid in dog and bovine thyroid slices. The increase in glucose oxidation is inhibited by 3- O-methyl-glucose, indicating that the glucose oxidized enters the cell via a stereospecific transport system. In sphingomyelinase-treated beef thyroids, there is a 65–90% fall in sphingomyelin content and a 10–30% fall in lecithin. Thus most of the sphingomyelin appears to be in the plasma membrane. Lecithinase C produced a small increase in glucose oxidation and phospholipid synthesis in only 7 of 15 experiments. In lecithinase C-treated tissue, the levels of all phospholipids fell about equally. Sphingomyelinase and lecithinase C, unlike thyroid-stimulating hormone, failed to induce the formation of intracellular colloid droplets in vitro, and Sphingomyelinase failed to produce a fall in the radioiodine content of chick thyroids.