Characterization of catechol-thioether-induced apoptosis in human SH-SY5Y neuroblastoma cells.

Abstract

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.

• Authors: Luciana Mosca, Italo Tempera, Eugenio Lendaro, Laura Di Francesco, Maria d'Erme
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 86 Issue 4 Pg. 954-60 (Mar 2008) ISSN: 1097-4547 [Electronic] United States
• PMID: 17929313 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2007 Wiley-Liss, Inc.

Chemical References

• Catechols
• Cysteinyldopa
• Cytochromes c
• Poly(ADP-ribose) Polymerases
• catechol
• Calcium

Topics

• Apoptosis (drug effects)
• Blotting, Western
• Calcium (metabolism)
• Catechols
• Cell Line, Tumor
• Cysteinyldopa (pharmacology)
• Cytochromes c (drug effects, metabolism)
• Humans
• Membrane Potentials (drug effects)
• Microscopy, Fluorescence
• Mitochondria (drug effects)
• Neuroblastoma
• Neurons (drug effects)
• Poly(ADP-ribose) Polymerases (drug effects, metabolism)
• Signal Transduction (drug effects, physiology)