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RESEARCH PRODUCT
Involvement of caspase-3 and GD3 ganglioside in ceramide-induced apoptosis in Farber disease.
Giorgio StassiGiovanni ZummoGiovanni PeriFelicia FarinaBucchieri FabioMatilde TodaroFrancesco Cappellosubject
AdultCeramidePathologymedicine.medical_specialtyHistologyColonCaspase 3ApoptosisCeramideschemistry.chemical_compoundGangliosidesmedicineGD3 gangliosideHumansIntestinal MucosaCaspaseFarber diseaseFarber diseaseTUNEL assaybiologyCaspase 3ApoptosiCell Biologymedicine.diseaseCeramidaseCaspaseK18EpitheliumActive caspase-3Lysosomal Storage Diseasesmedicine.anatomical_structurechemistryApoptosisCaspasesCancer researchbiology.proteinAnatomyActive caspase-3; Apoptosis; Caspases; Farber disease; GD3 ganglioside; K18; Anatomy; Cell Biologydescription
Farber's disease (FD) is a rare genetic disorder caused by ceramidase deficiency, which results in ceramide accumulation in lung, liver, colon, skeletal muscle, cartilage, and bone. Although this disease has been symptomatically characterized, little is known about its molecular pathogenetic process. Because recent studies reported that ceramide accumulation induces GD3 ganglioside formation and apoptosis, we investigated, in tissue obtained via colonoscopy from seriously involved patients, the possible involvement of ceramide in FD colonocyte destruction. Histochemical and TUNEL analyses of paraffin-embedded sections revealed that 45 ± 4.3% of FD colonocytes showed morphological signs of apoptosis compared with the 8 ± 2.3% of constitutive epithelial cell death. Importantly, immunohistochemical study for pro-apoptotic factors showed that GD3 accumulation co-localized with active caspase-3 and cleaved K18 in FD colon tissue. These findings provide evidence for a role of the apoptotic ceramide pathway in the pathogenesis of FD.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2000-02-01 | The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society |