Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurons (both primary cultures of 3-day rat hippocampal neurons and embryonic chick neurons) rapidly converted exogenous NBD-sphingomyelin (SM) to NBD-Cer but only slowly converted NBD-Cer to NBD-SM. This was confirmed by demonstrating low in vitro sphingomyelin synthase (SMS) and high sphingomyelinase (SMase) activity in neurons. Similar results were observed in a human neuroblastoma cell line (LA-N-5). In contrast, primary cultures of 3-day-old rat oligodendrocytes only slowly converted NBD-SM to NBD-Cer but rapidly converted NBD-Cer to NBD-SM. This difference was confirmed by high in vitro SMS and low SMase activity in neonatal rat oligodendrocytes. Similar results were observed in a human oligodendroglioma cell line. Mass-Spectrometric analyses confirmed that neurons had a low SM/Cer ratio of (1.5 : 1) whereas oligodendroglia had a high SM/Cer ratio (9 : 1). Differences were also confirmed by [(3)H]palmitate-labeling of ceramide, which was higher in neurons compared with oligodendrocytes. Stable transfection of human oligodendroglioma cells with neutral SMase, which enhanced the conversion of NBD-SM to NBD-Cer and increased cell death, whereas transfection with SMS1 or SMS2 enhanced conversion of NBD-Cer to NBD-SM and was somewhat protective against cell death. Thus, SMS rather than SMases may be more important for sphingolipid homeostasis in oligodendrocytes, whereas the reverse may be true for neurons.
 ...
PMID:Differential regulation of sphingomyelin synthesis and catabolism in oligodendrocytes and neurons. 1848 14

Oxidative stress plays a key role in brain injury after cerebral ischemia-reperfusion, which contributes toward excessive apoptosis of nerve cells. Therefore, it would be beneficial to identify a therapy that could interfere with the progression of apoptosis and protect the brain from ischemia-reperfusion injury. As ceramide, a well-known second messenger of apoptosis, can be metabolized by sphingomyelin synthase 1 (SMS1), recent research has focused on the link between SMS1 and apoptosis in different cells. To investigate whether SMS1 is involved in the process of oxidative stress-induced apoptosis in neurons and to explore the possible underlying mechanism, we treated mouse neuroblastoma Neuro-2A (N2a) cells with hydrogen peroxide (H2O2). Incubation with H2O2 significantly upregulated the expression of SMS1, increased the intracellular levels of ceramide and sphingomyelin synthase activity, and induced apoptosis. Moreover, pretreatment of N2a cells with D609, an sphingomyelin synthase inhibitor, or SMS1-silencing RNA (siRNA) further increased ceramide and potentiated H2O2-induced apoptosis which could be reversed by SB203580 (a p38 inhibitor). Thus, our study has shown that SMS1 regulates ceramide levels in N2a cells and plays a potent protective role in this oxidative stress-induced apoptosis partly through the p38 pathway.
 ...
PMID:Inhibition of sphingomyelin synthase 1 affects ceramide accumulation and hydrogen peroxide-induced apoptosis in Neuro-2a cells. 2739 27