RGD Reference Report - Transient mechanoactivation of neutral sphingomyelinase in caveolae to generate ceramide. - Rat Genome Database

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Transient mechanoactivation of neutral sphingomyelinase in caveolae to generate ceramide.

Authors: Czarny, M  Liu, J  Oh, P  Schnitzer, JE 
Citation: Czarny M, etal., J Biol Chem. 2003 Feb 14;278(7):4424-30. Epub 2002 Dec 6.
RGD ID: 1581395
Pubmed: PMID:12473648   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M210375200   (Journal Full-text)

The vascular endothelium acutely autoregulates blood flow in vivo in part through unknown mechanosensing mechanisms. Here, we report the discovery of a new acute mechanotransduction pathway. Hemodynamic stressors from increased vascular flow and pressure in situ rapidly and transiently induce the activity of neutral sphingomyelinase but not that acid sphingomyelinase in a time- and flow rate-dependent manner, followed by the generation of ceramides. This acute mechanoactivation occurs directly at the luminal endothelial cell surface primarily in caveolae enriched in sphingomyelin and neutral sphingomyelinase, but not acid sphingomyelinase. Scyphostatin, which specifically blocks neutral but not acid sphingomyelinase, inhibits mechano-induced neutral sphingomyelinase activity as well as downstream activation of extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK2) by increased flow in situ. We postulate a novel physiological function for neutral sphingomyelinase as a new mechanosensor initiating the ERK cascade and possibly other mechanotransduction pathways.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Smpd2Ratceramide biosynthetic process  IDA  RGD 
Smpd2Ratintracellular signal transduction  IMP  RGD 
Smpd2Ratresponse to mechanical stimulus  IMP  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Smpd2Ratcaveola  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Smpd2  (sphingomyelin phosphodiesterase 2)


Additional Information