Gliotoxin induces caspase-dependent neurite degeneration and calpain-mediated general cytotoxicity in differentiated human neuroblastoma SH-SY5Y cells.
2006 (English)In: Biochem Biophys Res Commun, ISSN 0006-291X, Vol. 345, no 3, 1068-74 p.Article in journal (Refereed) Published
In this study, a significant increase by 50% in intracellular free calcium concentration ([Ca(2+)](i)) was observed in differentiated human neuroblastoma (SH-SY5Y) cells after exposure to 0.25microM of the fungal metabolite gliotoxin for 72h. Further, the involvement of caspases and calpains was demonstrated to underlie the gliotoxin-induced cytotoxic and neurite degenerative effects. The caspase inhibitor Z-VAD-fmk almost completely reduced the neurite degeneration from 40% degeneration of neurites to 5% as compared to control. Inhibition of calpains with calpeptin significantly attenuated gliotoxin-induced cytotoxicity, determined as reduction in total cellular protein content, from 43% to 14% as compared to control cells. Western blot analyses of alphaII-spectrin breakdown fragments confirmed activity of the proteases, and that alphaII-spectrin was cleaved by caspases in gliotoxin-exposed cells. These results show that calpains and caspases have a role in the toxicity of gliotoxin in differentiated SH-SY5Y cells and that the process may be Ca(2+)-mediated.
Place, publisher, year, edition, pages
2006. Vol. 345, no 3, 1068-74 p.
Calcium/metabolism, Calpain/*metabolism, Caspases/*metabolism, Cell Differentiation, Cell Line;/pharmacology, Gliotoxin/*pharmacology, Humans, Immunosuppressive Agents/*pharmacology, Neurites/*metabolism, Neuroblastoma/*metabolism, Spectrin/metabolism
Pharmacology and Toxicology
IdentifiersURN: urn:nbn:se:su:diva-20495PubMedID: 16712786OAI: oai:DiVA.org:su-20495DiVA: diva2:187021