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Journal of Histochemistry and Cytochemistry, Vol. 48, 57-62, January 2000, Copyright © 2000, The Histochemical Society, Inc.

ARTICLE

Involvement of Caspase-3 and GD3 Ganglioside in Ceramide-induced Apoptosis in Farber Disease

Felicia Farinaa, Francesco Cappelloa, Matilde Todaroa, Fabio Bucchieria, Giovanni Peria, Giovanni Zummoa, and Giorgio Stassia
a Department of Surgical, Anatomical and Oncological Sciences, Human Anatomy Section, University of Palermo, Palermo, Italy

Correspondence to: Giorgio Stassi, Dept. of Surgical, Anatomical and Oncological Sciences, Human Anatomy Section, U. of Palermo, Via del Vespro 129, 90127 Palermo, Italy.

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. (J Histochem Cytochem 48:57–62, 2000)

Key Words: apoptosis, caspases, active caspase-3, GD3 ganglioside, K18, Farber disease


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