Acid sphingomyelinase

Acid Sphingomyelinase-derived Ceramide Signaling in Apoptosis... 

Cellular ceramide is generated either by hydrolysis of sphingomyelin or by de novo synthesis. Sphingomyelin hydrolysis is catalyzed by at least three different sphingomyelinases that are discriminated by their optimal pH acid, neutral, and alkaline sphingomyelinases. In the present manuscript we will focus on acid sphingomyelinase (ASM)-released ceramide. 

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NIEMANN-PICK DISEASE ACID SPHINGOMYELINASE DEFICIENCY... 

Injury to cell plasma membrane can activate acid sphingomyelinase to break down membrane lipid sphingomyelin and generate the second messenger ceramide, a complex lipid, to initiate the apoptosis (HI). Ceramide, perhaps through intracellular mitogen-activated protein kinases (MAPK), can alter cellular susceptibility to TNF-a, FasL, and ionizing radiation-induced apoptosis (HI, Wll). 

Pavlu-Pereira H, Asfaw B, Poupetova H, Ledvinova J, Sikora J, Vanier MT, Sandhoff K, Zeman J, Novaotna Z, Chudoba D, Elleder M (2005) Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study. J Inherit Metab Dis 28 203-227... 

Miranda, S. R., Erlich, S., Friedrich, V. L., Jr., Gatt, S. and Schuchman, E. H. (2000). Hematopoietic stem cell gene therapy leads to marked visceral organ improvements and a delayed onset of neurological abnormalities in the acid sphingomyelinase deficient mouse model of Niemann-Pick disease. Gene Ther. 7, 1768-1776. 

Acid sphingomyelinase is a lysosomal enzyme that catalyzes the breakdown of sphingomyelin to ceramide and phosphoryl-choline.A deficiency of this enzyme leads to lysosomal accumulation of sphingomyelin in patients with Niemann-Pick disease. Recent data indicate that correct intracellular targeting of acid sphingomyelinase to lysosomes is dependent on the mannose 6-phosphate-mediated pathway. Does this imply that the I-cell patient will present with Niemann-Pick symptoms Can I-cell disease be viewed as a constellation of many lysosomal storage diseases ... 

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