Comparison of S-nitrosoglutathione- and staurosporine-induced apoptosis in human neural cells

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DOIResolve DOI: https://doi.org/10.1139/cjpp-2014-0053
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Name affiliation
  1. National Research Council of Canada. Human Health Therapeutics
FormatText, Article
Journal titleCanadian Journal of Physiology and Pharmacology
ISSN0008-4212
1205-7541
Volume92
Issue12
Pages1001–1011
Subjectneural progenitors; caspase 3; caspase 8; BAX; BCL-XL; mitochondria; NT2; hNP1; SH-SY5Y
Abstract
S-nitrosoglutathione (GSNO) is an endogenously produced S-nitrosylating compound that controls the function of various proteins. While a number of rodent cell lines have been used to study GSNO-induced apoptosis, the mechanisms of action remain to be evaluated in human cells and in parallel with other common apoptosis-inducing agents. In this study, we compared the pro-apoptotic effects of GSNO and staurosporine (STS) on human neural progenitors (NT2, hNP1) and neuroblasts (SH-SY5Y). We show that these cells exhibit comparable levels of susceptibility to GSNO- and STS-induced apoptotic cell death, as demonstrated by condensed nuclei and CASP3 activation. Mechanistic differences in apoptotic responses were observed as differential patterns of DNA fragmentation and levels of BAX, BCL-XL, CASP8, and p-ERK in response to GSNO and STS treatment. Mitochondrial membrane potential analysis revealed that NT2 and hNP1 cells, but not SH-SY5Y cells, undergo mitochondrial hyperpolarization in response to short-term exposure to STS prior to undergoing subsequent depolarization. This is the first study to report differences in apoptotic responses to GSNO and STS in 3 complementary human neural cell lines. Furthermore, these cells represent useful tools in cell pharmacological paradigms in which susceptibility to apoptosis-inducing agents needs to be assessed at different stages of neural cell fate commitment and differentiation.
Publication date
PublisherCanadian Science Publishing
LanguageEnglish
Peer reviewedYes
NRC numberNRC-HHT-53227
NPARC number21275330
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