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

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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.
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Keywords: BAX; BCL-XL; Bax; NT2; SH-SY5Y; caspase 3; caspase 8; caspase-3; caspase-8; cellules souches neurales; hNP1; mitochondria; mitochondrie; neural progenitors

Document Type: Research Article

Affiliations: 1: Human Health Therapeutics, National Research Council Canada, 1200 Montreal Road, Ottawa, ON K1A 0R6, Canada. 2: Medicenna Therapeutics, Inc., Suite 1301--1500 West Georgia Street, Vancouver, BC V6G 2Z6, Canada.

Publication date: January 1, 2014

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