paperKB
coga / coga-kb
Help
Sign in

Chunk #1 — Introduction

Source
Mammalian neutral sphingomyelinases: regulation and roles in cell signaling responses.
Embedded
yes

Text

Among the bioactive species of sphingolipids, ceramide has been extensively studied and identified as an important signaling molecule in cell growth arrest, differentiation, senescence, apoptosis and inflammation (Chalfant and Spiegel, 2005; El Alwani et al., 2006; Hannun and Obeid, 2008; Modrak et al., 2006). A variety of stimuli including tumor necrosis factor-α (TNF-α), interleukin (IL)-1, daunorubicin and other chemotherapeutics can induce the formation of ceramide (Bartke and Hannun, 2009; Nikolova-Karakashian et al., 2008) and this can occur through several pathways including the de novo synthetic pathway (Perry, 2002), the ceramide salvage pathway (Kitatani et al., 2008) and the hydrolysis of complex sphingolipids such as sphingomyelin (SM) (Stoffel, 1999). Sphingomyelinase (SMase) hydrolyzes the phosphodiester bond of SM yielding ceramide and phosphocholine. Several isoforms of SMases have been identified and classified by their pH optima: acid SMase, alkaline SMase, and neutral SMases (nSMases). Of these, alkaline SMase is found in the intestinal tract and bile, and is thought to play a role in SM digestion (Duan, 2006). In contrast, acid SMase (SMPD1) comprises both a lysosomal enzyme and a secretory SMase and