title: Evidence for coordination of lysosomal (ASMase) and plasma membrane (NSMase2) forms of sphingomyelinase from mutant mice.
abstract: NSMase2 is associated to the plasma membrane, whereas ASMase is predominantly lysosomal; both hydrolyze sphingomyelin (SM) to ceramide and phosphocholine. Although SM accumulated in both ASMase(-/-) and fro/fro (NSMase2(-/-)) fibroblasts, the reduction of ceramides was more dramatic in fro/fro cells. ASMase mRNA, protein and enzyme activity were substantially elevated in fro/fro fibroblasts. In contrast, NSMase2 activity was unaffected in ASMase(-/-) fibroblasts. ASMase(-/-) cells showed normal cell cycling whereas fro/fro cells grew slowly and were arrested in G1/G0 and could be corrected by transfection with smpd3 gene. This suggests two distinct subcellular pathways for SM catabolism with distinct functions.
authors.affiliation: Department of Pediatrics, University of Chicago, Chicago, IL 60637, United States.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Qin
authors.forename: Glyn
authors.initials: G
authors.lastname: Dawson
mesh_terms: D000818:Animals; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000235:genetics; D002462:Cell Membrane / Q000201:enzymology*; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D005434:Flow Cytometry; D016193:G1 Phase / Q000235:genetics; D020869:Gene Expression Profiling; D008247:Lysosomes / Q000201:enzymology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D010767:Phosphorylcholine / Q000378:metabolism; D016192:Resting Phase, Cell Cycle / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013108:Sphingomyelin Phosphodiesterase / Q000235:genetics* / Q000378:metabolism; D013109:Sphingomyelins / Q000378:metabolism
chemical_list: D002518:Ceramides; D013109:Sphingomyelins; D010767:Phosphorylcholine; C577975:ASMase, mouse; C491483:Smpd3 protein, mouse; D013108:Sphingomyelin Phosphodiesterase