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Characterization of catechol‐thioether‐induced apoptosis in human SH‐SY5Y neuroblastoma cells
Author(s) -
Mosca Luciana,
Tempera Italo,
Lendaro Eugenio,
Di Francesco Laura,
d'Erme Maria
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21536
Subject(s) - sh sy5y , thioether , apoptosis , neuroblastoma , catechol , chemistry , microbiology and biotechnology , cancer research , biochemistry , biology , cell culture , stereochemistry , genetics
Recent work has highlighted the involvement of a dopamine derivative, 5‐S‐cysteinyl‐dopamine (CysDA), in neurodegeneration and apoptotic cell death. In this paper we study in further detail the apoptotic process activated by this catechol‐thioether derivative of dopamine in SH‐SY5Y neuroblastoma cells. CysDA activates a cascade of events by an initial perturbation of Calcium homeostasis in the cell. Cell treatment with the catechol‐thioether induces an immediate rise in intracellular Ca 2+ concentration, as demonstrated by a shift in the indo‐1 dye emission spectrum, and a sustained high calcium concentration at long times of incubation. Fluorescence microscopy data show that the treatment of cells induces mitochondrial transmembrane potential depolarization, a clear evidence of the onset of apoptotic process. Programmed cell death activation is also demonstrated by cytochrome c release from the mitochondria, by an increased activity of both caspase‐8 and ‐9 and by the poly(ADP‐ribose)polymerase (PARP‐1) cleavage, yielding the typical 86 kDa fragment due to caspase‐3 activity. Overall, our data support the hypothesis that CysDA may induce apoptotic death in neuronal cells, via an initial perturbation of calcium homeostasis in the cytosol. © 2007 Wiley‐Liss, Inc.