May be of interest..
Link:
http://www.ncbi.nlm....9&dopt=CitationActivation of sphingolipid turnover and chronic generation of ceramide and sphingosine in liver during aging.Lightle SA, Oakley JI, Nikolova-Karakashian MN.
Department of Physiology, University of Kentucky College of Medicine, Chandler Medical Center, MS 579, 800 Rose Street, Lexington, KY 40536, USA.
Aging leads to a decreased ability of liver to metabolize drugs and increased expression and secretion of acute phase proteins, such as serum amyloid A (SAA), C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP). This phenomenon resembles some aspects of the acute phase response of host to inflammation; however, the molecular basis for the similarity is unclear. Ceramide and sphingosine are second messenger mediators of cellular responses to stress and inflammation. In liver, they play important role in mediating acute phase responses to IL1-beta. In this study, we use HPLC and thin layer chromatography to evaluate the effects of aging on steady-state levels of ceramide and sphingosine. We report that both lipids are elevated in liver of old (24 months) as compared to young (5 months) male Fisher 344 rats. To elucidate the mechanism(s) for ceramide elevation, we test the acidic (ASMase) and neutral sphingomyelinase (NSMase) in vitro using NBD-sphingomyelin as an exogenous substrate. SM synthase is also analyzed in vitro using NBD-ceramide and [3H]-dipalmitoylphosphatidylcholine (DPPC) as exogenous substrates. In accordance with the increases in the mass of ceramide, the activity of acid and neutral SMase is elevated in old animals. Michaelis-Menten analysis of NSMase implies that the apparent activation of this enzyme is caused by an increase in the Vmax of the enzyme. In contrast, SM synthase activity is lower in old animals as compared to young ones. These results show that aging is accompanied by an elevation in SM turnover and a decrease in its synthesis, resulting in accumulation of pro-inflammatory and growth inhibitory second messenger ceramide. Ceramidase, the only enzyme leading to sphingosine generation, is also measured in vitro using NBD-ceramide as a substrate and liver homogenate as an enzyme source. Its activity is higher in the old rats, as compared to young ones. The acid and neutral forms of the enzyme are affected the most, while the changes in the alkaline enzyme are not significant. The increases in the basal levels of ceramide and sphingosine in old animals may contribute to the onset of an inflammatory like state in liver during aging, exemplified by decreased P4502C11 mRNA expression and chronic induction of acute phase protein expression.
Link:
http://www.ncbi.nlm....6&dopt=Citation
Ceramide induces expression of the senescence histochemical marker, beta-galactosidase, in human fibroblasts.Mouton RE, Venable ME.
Biology Department, Appalachian State University, Boone, NC 28608-2027, USA.
We recently showed that ceramide is elevated in senescence and that when administered to low-passage cells induces biochemical changes characteristic of senescence. The in situ histochemical marker beta-galactosidase (beta-Gal) has provided an important tool in the study of cellular senescence. We investigated the ability of ceramide to induce the expression of beta-Gal and correlated this with cell proliferation. We find that D-e-C6-ceramide, induces the expression of acidic beta-Gal in fetal lung-derived Wi-38 human diploid fibroblasts. Our results show that this induction is: (1) time and concentration dependent; and (2) reversible upon ceramide removal. We also find that concomitant with the onset of beta-Gal staining, DNA synthesis is blocked. These conditions are reversible. The induction of beta-Gal expression is specific to C6-ceramide. We discuss a potential role of beta-Gal in the regulation of senescence. Although signal transduction of senescence is still not fully understood, this new evidence strengthens the hypothesis that ceramide plays a key role in signaling down stream biochemical changes in cellular senescence.